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Wu CS, Li HP, Hsieh CH, Lin YT, Yi-Feng Chang I, Chung AK, Huang Y, Ueng SH, Hsiao YC, Chien KY, Luo JD, Chen CH, Liao WC, Hung JL, Yuan SN, OuYang CN, Chiang WF, Chien CY, Chuang HC, Chu LJ, Liu H, Yang CY, Robles AI, Rodriguez H, Lin HH, Yang HY, Hsueh C, Chang KP, Yu JS, Chang YS. Integrated multi-omics analyses of oral squamous cell carcinoma reveal precision patient stratification and personalized treatment strategies. Cancer Lett 2025; 614:217482. [PMID: 39842500 DOI: 10.1016/j.canlet.2025.217482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/10/2025] [Accepted: 01/17/2025] [Indexed: 01/24/2025]
Abstract
Oral cavity squamous cell carcinoma (OSCC), a leading subtype of head and neck cancer, exhibits high global incidence and mortality rates. Despite advancements in surgery and radiochemotherapy, approximately one-third of patients experience relapse. To improve current targeted and immunotherapy strategies for recurrent OSCC, we conducted multi-omics analyses on pretreatment OSCC samples (cohorts 1 and 2, n = 137) and identified A3A and EGFR, both at the RNA and protein levels, as inversely expressed markers for patient stratification and response prediction. Survival analysis demonstrated that elevated A3A or PD-L1 expression levels correlated to improved responses to anti-PD-1 therapy in patients (cohort 3a, n = 50, IHC). In contrast, high RRAS expression (cohort 4, n = 252, qRT-PCR) was significantly associated with OSCC recurrence. Cell-based experiments revealed that RRAS was involved in radiotherapy and cisplatin resistance through the EGFR/RRAS/AKT/ERK signaling pathway. In OSCC patient-derived xenograft (PDX) mouse models, treatments with cisplatin and cetuximab (anti-EGFR) effectively reduced tumor size in EGFR-high-derived (#34) but not A3A-high-derived (#22) PDX tumors. Our study demonstrated that A3A-high tumors were immune-hot and responsive to anti-PD-1 therapy, whereas EGFR-high tumors exhibited chr.7p11.2 gains and DNA repair alterations. Additionally, RRAS-high tumors were associated with OSCC recurrence via AKT and ERK phosphorylation and demonstrate improved clinical outcomes with cetuximab therapy (cohort 3b, n = 49, IHC). This study emphasizes the significance of A3A and EGFR expression levels in OSCC patient stratification and precision therapy, suggesting the use of anti-PD-1 or anti-EGFR treatments, respectively based on these biomarkers. Furthermore, RRAS emerges as a novel prognostic marker for local recurrence.
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Affiliation(s)
- Chi-Sheng Wu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Hsin-Pai Li
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Microbiology and Immunology, Chang Gung University, Taoyuan City, 33302, Taiwan; Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, at Linkou, Taoyuan City, 33305, Taiwan.
| | - Chia-Hsun Hsieh
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, at Linkou, Taoyuan City, 33305, Taiwan; Division of Hematology-Oncology, Department of Internal Medicine, New Taipei Municipal City TuCheng Hospital, New Taipei City, Taiwan; College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Yu-Tsun Lin
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Ian Yi-Feng Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan City, 33305, Taiwan
| | - An-Ko Chung
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Yenlin Huang
- Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; School of Medicine, National Tsing-Hua University, Hsinchu, 300044, Taiwan; Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, at Linkou, Taoyuan City, 33305, Taiwan
| | - Shir-Hwa Ueng
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Yung-Chin Hsiao
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan
| | - Kun-Yi Chien
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Ji-Dung Luo
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Bioinformatics Resource Center, The Rockefeller University, 1230 York Avenue, New York City, NY, USA, 10065
| | - Chia-Hua Chen
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Anatomy, School of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Wei-Chao Liao
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Jui-Lung Hung
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Sheng-Ning Yuan
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Chun-Nan OuYang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Wei-Fan Chiang
- Department of Dentistry, Chi-Mei Medical Center, Liouying, Taiwan; School of Dentistry, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan
| | - Chih-Yen Chien
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hui-Ching Chuang
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Lichieh Julie Chu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Hsuan Liu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan; Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Chia-Yu Yang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; Department of Microbiology and Immunology, Chang Gung University, Taoyuan City, 33302, Taiwan
| | - Ana I Robles
- Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA
| | - Henry Rodriguez
- Office of Cancer Clinical Proteomics Research, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA
| | - Hsi-Hsien Lin
- Department of Microbiology and Immunology, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Keelung, Keelung, 20401, Taiwan
| | - Huang-Yu Yang
- College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Nephrology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Chuen Hsueh
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan
| | - Kai-Ping Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan.
| | - Jau-Song Yu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan; Liver Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan City, 33305, Taiwan.
| | - Yu-Sun Chang
- Molecular Medicine Research Center, Chang Gung University, Taoyuan City, 33302, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan
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Spirito F, Nocini R, Mori G, Albanese M, Georgakopoulou EA, Sivaramakrishnan G, Khalil B, Špiljak B, Surya V, Mishra D, Chaurasia A. The Potential of Oncolytic Virotherapy in the Treatment of Head and Neck Cancer: A Comprehensive Review. Int J Mol Sci 2024; 25:12990. [PMID: 39684701 DOI: 10.3390/ijms252312990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/21/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
Head and neck cancer (HNC) represents a challenging oncological entity with significant morbidity and mortality rates. Despite advances in conventional therapies, including surgery, chemotherapy, and radiation therapy, the overall survival rates for advanced HNC remain suboptimal. In recent years, the emerging field of oncolytic virotherapy has gained attention as a promising therapeutic approach for various malignancies, including HNC. This review provides a comprehensive overview of the current understanding of oncolytic viruses (Ovs) in the context of HNC treatment, including their mechanisms of action, preclinical and clinical studies, challenges, and future directions. Future oncolytic virotherapy focuses on improving delivery and specificity through nanoparticle carriers and genetic modifications to enhance tumor targeting and immune response. Combining different OVs and integrating them with immunotherapies, such as checkpoint inhibitors, could overcome tumor resistance and improve outcomes. Personalized approaches and rigorous clinical trials are key to ensuring the safety and effectiveness of virotherapy in treating HNC.
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Affiliation(s)
- Francesca Spirito
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Riccardo Nocini
- Department of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, University of Verona, 37134 Verona, Italy
| | - Giorgio Mori
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Massimo Albanese
- Department of Surgical Sciences, Dentistry, Gynaecology and Paediatrics, University of Verona, 37134 Verona, Italy
| | - Eleni A Georgakopoulou
- Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | | | - Basel Khalil
- Department of Basic Sciences, Faculty of Dentistry, University of Damascus, Damascus 30621, Syria
| | - Bruno Špiljak
- Department of Oral Medicine, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Varun Surya
- Department of Oral Pathology and Microbiology, Centre for Dental Educationand Research, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Deepika Mishra
- Department of Oral Pathology and Microbiology, Centre for Dental Educationand Research, All India Institute of Medical Sciences, New Delhi 110029, India
| | - Akhilanand Chaurasia
- Department of Oral Medicine and Radiology, King George's Medical University, Lucknow 226003, India
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Chagas PS, Garcia CB, Sousa LO, da Silva G, de Sousa GR, Marcelino RC, de Matos LL, Kowalski LP, Salles É, Wang L, Baban B, Leopoldino AM. SIGMAR1 Knockdown Enhances Oral Cancer Cell Chemosensitivity to Cisplatin via Decreased PD-L1 Expression. Int J Mol Sci 2024; 25:11856. [PMID: 39595926 PMCID: PMC11594079 DOI: 10.3390/ijms252211856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 07/07/2024] [Accepted: 07/10/2024] [Indexed: 11/28/2024] Open
Abstract
Emerging evidence suggests that aberrant expression levels of Sigma1 (SIGMAR1, also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer.
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Affiliation(s)
- Pablo Shimaoka Chagas
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
- Department of Oral Biology and Diagnostic Services, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA; (É.S.); (L.W.); (B.B.)
| | - Cristiana Bernadelli Garcia
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
| | - Lucas Oliveira Sousa
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
| | - Gabriel da Silva
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
| | - Graziella Ribeiro de Sousa
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
| | - Rodolfo Cabral Marcelino
- Laboratory of Molecular Modeling and Computer Simulation/MolMod-CS, Institute of Chemistry, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil;
| | - Leandro Luongo de Matos
- Head and Neck Surgery Department, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, University of São Paulo Medical School (ICESP HCFMUSP), São Paulo 01246-000, SP, Brazil;
- Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05653-120, SP, Brazil
| | - Luiz Paulo Kowalski
- Head and Neck Surgery Department, University of São Paulo Medical School, São Paulo 05403-000, SP, Brazil;
- Head and Neck Surgery Department, A. C. Camargo Cancer Center, São Paulo 01525-001, SP, Brazil
| | - Évila Salles
- Department of Oral Biology and Diagnostic Services, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA; (É.S.); (L.W.); (B.B.)
| | - Lei Wang
- Department of Oral Biology and Diagnostic Services, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA; (É.S.); (L.W.); (B.B.)
- Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Babak Baban
- Department of Oral Biology and Diagnostic Services, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA; (É.S.); (L.W.); (B.B.)
- Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Andréia Machado Leopoldino
- Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/n, Ribeirão Preto 14040-903, SP, Brazil; (C.B.G.); (L.O.S.); (G.d.S.); (G.R.d.S.); (A.M.L.)
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Jiang K, Zhu M, He S, Wang C, Wang Y, Ren Y, Xiang Z, Chen Y. The clinical outcomes of induction chemotherapy followed by radiotherapy vs. chemoradiotherapy in locally advanced hypopharyngeal squamous cell carcinoma: A retrospective study. Heliyon 2024; 10:e38811. [PMID: 39498037 PMCID: PMC11533557 DOI: 10.1016/j.heliyon.2024.e38811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/30/2024] [Accepted: 09/30/2024] [Indexed: 11/07/2024] Open
Abstract
Background Stage III and IVA-B hypopharyngeal carcinoma presents a substantial risk of recurrence and metastasis. The treatment strategy remains uncertain. The objective of this observational study was to compare the outcomes of induction chemotherapy followed by radiotherapy (ICRT) and induction chemotherapy followed by chemoradiotherapy (ICCRT) in the treatment of locally advanced hypopharyngeal squamous cell carcinoma. Methods 58 patients with stage III and IVA-B hypopharyngeal squamous cell carcinoma treated with ICRT (n = 26) or ICCRT (n = 32) were enrolled in the study. Baseline variables and toxicity rates were compared by Chi-squared test. Survival curves were constructed by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazard analysis was performed to evaluate the potential survival effects. Results There were no significant differences in gender, age, smoking, drinking, T category, N category, overall stage, induction chemotherapy schemes and cycles between the two groups. The median follow-up time was 36.3 months (range, 2.3-97.5 months). The 2-year recurrence-free survival (RFS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and the 1-year, 2-year overall survival (OS) expressed no significant differences between the two groups. Furthermore, induction chemotherapy regimen of TPF achieved better OS than TP or PF (hazard ratio [HR] 0.395, 95 % confidence interval [CI] 0.178-0.879; P = 0.023), OS of patients in N2-3 category was worse than N0-1 (HR 2.594, 95 % CI 1.230-5.471; P = 0.012). In addition, the grade 3-4 therapy-associated toxicities during radiotherapy were higher in the chemoradiotherapy group than in radiotherapy alone group (P = 0.020). Conclusion Following induction chemotherapy in patients with stage III/IVA-B hypopharyngeal squamous cell carcinoma, the concurrent chemoradiotherapy regimen provided similar survival rates with radiotherapy alone. Meanwhile, the incidence of treatment-related side effects during radiotherapy after induction chemotherapy were lower than that during chemoradiotherapy.
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Affiliation(s)
- Ke Jiang
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Meiyan Zhu
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shasha He
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chengtao Wang
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yan Wang
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yufeng Ren
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zijun Xiang
- Country Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yong Chen
- Country Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Pradhan R, Paul S, Acharya SS, Sinha S, Dash SR, Kundu CN. Nano formulated Resveratrol inhibits PD-L1 in oral cancer cells by deregulating the association between tumor associated macrophages and cancer associated fibroblasts through IL-6/JAK2/STAT3 signaling axis. J Nutr Biochem 2024; 125:109568. [PMID: 38185347 DOI: 10.1016/j.jnutbio.2024.109568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 12/30/2023] [Accepted: 01/03/2024] [Indexed: 01/09/2024]
Abstract
Tumor associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) in the tumor microenvironment secrete several cytokines, which involved in tumor initiation, progression, metastatic outgrowth and angiogenesis. However, the association between TAMs and CAFs in the context of tumor development remain unclear. Here, we studied the relationship between TAMs and CAFs along with the involvement of cytokines in the production of cancer-stem-like-cells (CSCs) in oral cancer cells and explored the potential anticancer effects of Nano-formulated Resveratrol (Res-NP) using an activated macrophage-M1 (AM-M1) and activated fibroblast cells as the model system. IL-6 secretion was found to be enhanced in the conditioned-medium (CM) when AM-M1 cells + CAFs-like cells were cocultured together. CSCs-enriched population was developed after addition of CM of AM-M1 +CAFs in H-357 cells and patient-derived-primary-oral-cancer cells. AM-M1 cells+ CAFs-like cells secreted IL-6 enhanced CSCs growth, proliferation, metastasis, and angiogenesis. IL-6 was found to promote PD-L1 expression in CSCs-enriched cells via JAK2/STAT3 pathway, as evident from the enhanced expression of p-JAK2 and p-STAT3. Nevertheless, Res-NP inhibited CSCs proliferation and reduced the expression of metastatic and angiogenic markers, in ovo blood vascularization, NO production and MMPs expression. Res-NP delinked the association between AM-M1 and CAFs by blocking IL-6 production and also disrupted the potential connection between IL-6 and PD-L1 with considerable decrease in p-JAK2 and p-STAT3 expressions. IL-6 depletion inhibited stemness and angiogenesis in oral CSCs by downregulating PD-L1 via JAK2/STAT3 cascade. Similar observations were also observed in Res-NP treated xenograft mice. Thus, data demonstrate that CSCs growth is dependent on IL-6/PD-L1 axis. Res-NP deregulates the association between AM-M1 and CAFs along-with attenuates carcinogenesis in in vitro, in ovo, ex vivo and in vivo model systems by inhibiting PD-L1 via IL-6/JAK2/STAT3 axis.
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Affiliation(s)
- Rajalaxmi Pradhan
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
| | - Subarno Paul
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
| | - Sushree Subhadra Acharya
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
| | - Saptarshi Sinha
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
| | - Somya Ranjan Dash
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India
| | - Chanakya Nath Kundu
- Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology, Deemed to be University, Bhubaneswar, Odisha, India.
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Cheng Y, Song Z, Chen J, Tang Z, Wang B. Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods. Heliyon 2024; 10:e25895. [PMID: 38380036 PMCID: PMC10877294 DOI: 10.1016/j.heliyon.2024.e25895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 02/05/2024] [Indexed: 02/22/2024] Open
Abstract
Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC. Further, it explores the mechanisms involved in the interaction of this pathway with exosomes and protein-protein interactions, and concludes with potential future OSCC therapeutic strategies.
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Affiliation(s)
- Yuxi Cheng
- Xiangya Stomatological Hospital, Central South University, Changsha, 410008, China
- Xiangya School of Stomatology, Central South University, Changsha, 410008, China
- Clinical Research Center of Oral Major Diseases and Oral Health, 410008, Hunan, China
| | - Zhengzheng Song
- Xiangya Stomatological Hospital, Central South University, Changsha, 410008, China
- Xiangya School of Stomatology, Central South University, Changsha, 410008, China
- Clinical Research Center of Oral Major Diseases and Oral Health, 410008, Hunan, China
| | - Juan Chen
- Xiangya Stomatological Hospital, Central South University, Changsha, 410008, China
- Xiangya School of Stomatology, Central South University, Changsha, 410008, China
- Clinical Research Center of Oral Major Diseases and Oral Health, 410008, Hunan, China
| | - Zhangui Tang
- Xiangya Stomatological Hospital, Central South University, Changsha, 410008, China
- Xiangya School of Stomatology, Central South University, Changsha, 410008, China
- Clinical Research Center of Oral Major Diseases and Oral Health, 410008, Hunan, China
| | - Baisheng Wang
- Xiangya Stomatological Hospital, Central South University, Changsha, 410008, China
- Xiangya School of Stomatology, Central South University, Changsha, 410008, China
- Clinical Research Center of Oral Major Diseases and Oral Health, 410008, Hunan, China
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Hanroongsri J, Amornphimoltham P, Younis RH, Chaisuparat R. Expression of PD-L1 and p-RPS6 in epithelial dysplasia and squamous cell carcinoma of the oral cavity. FRONTIERS IN ORAL HEALTH 2024; 5:1337582. [PMID: 38370876 PMCID: PMC10869481 DOI: 10.3389/froh.2024.1337582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 01/02/2024] [Indexed: 02/20/2024] Open
Abstract
Introduction Oral squamous cell carcinoma (OSCC) is often preceded by oral epithelial dysplasia (OED). The role of ribosomal protein S6 (RPS6) and programmed cell death ligand-1 (PD-L1) in the progression of OED to OSCC remains unclear. This study aimed to investigate the expression of phosphorylated RPS6 (p-RPS6) and PD-L1 in OSCC and OED and to examine its relationship with clinicopathological features. Methods Fifty-two OSCC and 48 OED cases were recruited for immunohistochemical analysis of p-RPS6 and PD-L1 expression. The expression of markers was correlated with clinicopathological features of OSCC and OED. Results We found p-RPS6 expression in all cases of OSCC and OED, whereas PD-L1 was expressed in 42/48 (87%) OED and in 28/52 (53%) OSCC. The patients with mild OED presented higher expression level of PD-L1 and p-RPS6 significantly, when compared to moderate-differentiated OSCC patients (p < 0.05). Moreover, we found a significant positive correlation between PD-L1 and p-RPS6 expression in OED and OSCC patients (p < 0.01). The PD-L1 expression was significantly related to more than 2 cm tumor size in OSCC patients (p = 0.007). Discussion Our findings suggest the upregulation of PD-L1 may be related with activation of the mTOR pathway in the early events of tumor progression and the pathogenesis of OSCC.
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Affiliation(s)
- Jaruwat Hanroongsri
- Division of Oral Diagnostic Sciences, Faculty of Dentistry, Thammasat University, Pathumthani, Thailand
| | | | - Rania H. Younis
- Department of Oral Pathology, Faculty of Dentistry, Alexandria University, Alexandria, Egypt
| | - Risa Chaisuparat
- Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
- Avatar Biotechnologies for Oral Heath and Healthy Longevity, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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Ma L, Qin N, Wan W, Song S, Hua S, Jiang C, Li N, Huang L, Gao X. TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma. Am J Physiol Cell Physiol 2024; 326:C362-C381. [PMID: 38105756 DOI: 10.1152/ajpcell.00061.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 12/19/2023]
Abstract
Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.
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Affiliation(s)
- Liwei Ma
- Department of Oral Medicine, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Niuyu Qin
- Department of Oral Medicine, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
| | - Wendong Wan
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
| | - Saiwen Song
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
| | - Siqi Hua
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
| | - Canhua Jiang
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ning Li
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Long Huang
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xing Gao
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Oral and Maxillofacial Cancer (COMAC), Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, China
- Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Todoroki K, Abe Y, Matsuo K, Nomura H, Kawahara A, Nakamura Y, Nakamura M, Seki N, Kusukawa J. Prognostic effect of programmed cell death ligand 1/programmed cell death 1 expression in cancer stem cells of human oral squamous cell carcinoma. Oncol Lett 2024; 27:79. [PMID: 38249811 PMCID: PMC10797318 DOI: 10.3892/ol.2024.14213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 12/12/2023] [Indexed: 01/23/2024] Open
Abstract
The relationship between cancer stem cells (CSCs) in oral squamous cell carcinoma (OSCC) and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) remains unclear. Therefore, the present study aimed to clarify the association between the CD44v3high/CD24low immunophenotype of CSCs in OSCC and PD-L1/PD-1 co-expression, and to assess the prognostic effect of CSCs in terms of immune checkpoint molecules. Formalin-fixed, paraffin-embedded tissue samples and clinicopathological data from 168 patients with OSCC were retrospectively retrieved. Immunohistochemical staining and reverse transcription quantitative polymerase chain reaction were applied to a tissue microarray of the invasive front of each case. Semi-automated cell counting was used to assess CD44v3, CD24, PD-L1 and PD-1 expression by immunohistochemistry (IHC) using a digital image analysis program. Associations between immunological markers and clinicopathological variables were estimated. Patients with the CSC immunophenotype CD44v3high/CD24low, and patients with a high PD-L1/PD-1-positive cell density in the tumor parenchyma and stroma had significantly lower survival rates. Furthermore, patients with the CSC immunophenotype (CD44v3high/CD24low) and high PD-L1/PD-1 co-expression had even lower survival rates (P<0.01, log-rank test). Notably, there was a positive correlation between CD44v3 and PD-L1 expression (τ=0.1096, P=0.0366, Kendall rank correlation coefficient) and a negative correlation between CD24 and PD-1 expression (τ=-0.1387, P=0.0089, Kendall rank correlation coefficient). Additionally, the high CD44v3 expression group, as determined by IHC, exhibited significantly decreased expression of U2 small nuclear RNA auxiliary factor 1 (U2AF1) at the mRNA level compared with that in the low CD44v3 expression group (P<0.001, Mann-Whitney U test), and U2AF1 and PD-L1 mRNA expression exhibited a significant negative correlation (τ=-0.3948, P<0.001, Kendall rank correlation coefficient). In conclusion, CSCs in OSCC may evade host immune mechanisms and maintain CSC stemness via PD-L1/PD-1 co-expression, resulting in unfavorable clinical outcomes.
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Affiliation(s)
- Keita Todoroki
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
- Department of Dental and Oral Surgery, Takagi Hospital, Kouhoukai Medical Corporation, Okawa, Fukuoka 831-0016, Japan
| | - Yushi Abe
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
- Department of Dental and Oral Surgery, Takagi Hospital, Kouhoukai Medical Corporation, Okawa, Fukuoka 831-0016, Japan
| | - Katsuhisa Matsuo
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
- Department of Dental and Oral Surgery, Takagi Hospital, Kouhoukai Medical Corporation, Okawa, Fukuoka 831-0016, Japan
| | - Hidetoshi Nomura
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Akihiko Kawahara
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Yoshiaki Nakamura
- Department of Dentistry and Oral Surgery, Oita Saiseikai Hita Hospital, Hita, Oita 877-1292, Japan
| | - Moriyoshi Nakamura
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Naoko Seki
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Jingo Kusukawa
- Dental and Oral Medical Center, Kurume University, School of Medicine, Kurume, Fukuoka 830-0011, Japan
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10
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Ren J. Bromodomain-containing protein 4 inhibition improves the efficacy of cisplatin and radiotherapy in oral squamous cell carcinoma by suppressing programmed cell death-ligand 1 expression. Basic Clin Pharmacol Toxicol 2024; 134:272-283. [PMID: 38014458 DOI: 10.1111/bcpt.13962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 09/01/2023] [Accepted: 09/16/2023] [Indexed: 11/29/2023]
Abstract
The bromodomain-containing protein 4 (BRD4) is highly expressed in oral squamous cell carcinoma (OSCC) and plays a crucial role in tumour progression. However, the impact of BRD4 on the efficacy of chemotherapy and radiotherapy by regulating the expression of programmed cell death-ligand 1 (PD-L1) in OSCC remains unclear. In this study, we found that the BRD4 inhibitor JQ1 effectively enhanced the inhibitory effects of cisplatin and radiotherapy on cell proliferation and promoted the apoptosis of OSCC cells by cisplatin and radiotherapy. Furthermore, treatment with JQ1 reversed the increase of the expression of PD-L1 by cisplatin and radiotherapy, whereas the overexpression of PD-L1 partially countered the beneficial effects of JQ1 on the anticancer efficacy of cisplatin and radiotherapy. These results demonstrate that the inhibition of BRD4 improves the anticancer effect of chemotherapy and radiotherapy by suppressing the expression of PD-L1 in OSCC, suggesting that targeting BRD4 could be a promising therapeutic approach for chemo/radioresistant OSCC.
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Affiliation(s)
- Jiajie Ren
- Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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11
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Steen S, Semmelmayer K, Flechtenmacher C, Hoffmann J, Freier K, Horn D, Hess J, Freudlsperger C, Moratin J. Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma. Int J Mol Sci 2023; 24:16386. [PMID: 38003576 PMCID: PMC10671831 DOI: 10.3390/ijms242216386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.
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Affiliation(s)
- Sonja Steen
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Karl Semmelmayer
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Christa Flechtenmacher
- Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Tissue Bank of the National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Jürgen Hoffmann
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Kolja Freier
- Department of Oral and Maxillofacial Surgery, Saarland University Hospital, 66421 Homburg, Germany; (K.F.)
| | - Dominik Horn
- Department of Oral and Maxillofacial Surgery, Saarland University Hospital, 66421 Homburg, Germany; (K.F.)
| | - Jochen Hess
- Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany;
- Research Group Molecular Mechanisms of Head and Neck Tumors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Christian Freudlsperger
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
| | - Julius Moratin
- Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; (S.S.); (K.S.); (J.H.); (C.F.)
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12
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Cichowska-Cwalińska N, Bieńkowski M, Popęda M, Dróżka M, Rutkowski J, Jassem J, Zaucha R. Radiotherapy-induced dynamic changes in the lymphocyte-to-monocyte ratio in patients with laryngeal cancer indicate poor prognosis. Front Oncol 2023; 13:1234953. [PMID: 37886164 PMCID: PMC10598385 DOI: 10.3389/fonc.2023.1234953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/20/2023] [Indexed: 10/28/2023] Open
Abstract
Aim We hypothesized that markers of inflammation correlate with response to radiotherapy in patients with non-metastatic laryngeal cancer (LC). Our aim was to assess peripheral and local markers of inflammation including lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), infiltrating CD8+ lymphocytes (TILsCD8), and programmed death 1 ligand (PD-L1) expression. Methods We performed a retrospective single-center analysis of LC patients administered definitive (R-RT) or postoperative radiotherapy (PORT). The primary endpoint was overall survival (OS) in relation to peripheral and local inflammatory markers and their dynamic changes during RT. Results Study group included 215 patients (R-RT, n=116; PORT, n=99). The baseline (t0) NLR and LMR were significantly correlated with OS in the R-RT group. In patients with high and low NLR at t0, the five-year OS was 33% and 56% (p=0.010) and in high and low LMR at t0, the five-year OS was 56% and 27% (p=0.003), respectively. The LMR increase during R-RT predicted better prognosis: the five-year OS in high and low LMR was 57% and 31% at t2 (after 2 weeks of RT) (p=0.015), 49% and 26% at t4 (p< 0.001), and 50% and 25% at t6 (p=0.013), respectively. Multivariable analysis shows that the worse performance status (p=0.003), the presence of nodal metastases (p=0.0001), and low baseline LMR (p=0.049) in the R-RT group, and the presence of nodal metastases (p=0.035) and completion treatment on time (p=0.042) in PORT group were associated with poor prognosis. The PD-L1 expression had no significant prognostic value in any of the examined patients. Conclusion The baseline LMR and its dynamic changes during R-RT and baseline NLR are independent prognostic factors in patients with nonmetastatic LC. PD-L1 expression and number of TILsCD8 have no prognostic value in R-RT and PORT group.
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Affiliation(s)
- Natalia Cichowska-Cwalińska
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
- Early Phase Clinical Trials Centre, Medical University of Gdańsk, Gdańsk, Poland
| | - Michał Bieńkowski
- Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland
| | - Marta Popęda
- Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland
| | - Magdalena Dróżka
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
| | - Jacek Rutkowski
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
| | - Jacek Jassem
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
| | - Renata Zaucha
- Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
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Joshi P, Waghmare S. Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges. World J Stem Cells 2023; 15:438-452. [PMID: 37342225 PMCID: PMC10277967 DOI: 10.4252/wjsc.v15.i5.438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 02/21/2023] [Accepted: 04/07/2023] [Indexed: 05/26/2023] Open
Abstract
Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates. Amongst oral cavity cancers, tongue carcinoma is a very common and aggressive oral cavity carcinoma. Despite the implementation of a multimodality treatment regime including surgical intervention, chemo-radiation as well as targeted therapy, tongue carcinoma shows a poor overall 5-year survival pattern, which is attributed to therapy resistance and recurrence of the disease. The presence of a rare population, i.e., cancer stem cells (CSCs) within the tumor, are involved in therapy resistance, recurrence, and distant metastasis that results in poor survival patterns. Therapeutic agents targeting CSCs have been in clinical trials, although they are unable to reach into therapy stage which is due to their failure in trials. A more detailed understanding of the CSCs is essential for identifying efficient targets. Molecular signaling pathways, which are differentially regulated in the CSCs, are one of the promising targets to manipulate the CSCs that would provide an improved outcome. In this review, we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.
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Affiliation(s)
- Priyanka Joshi
- Stem Cell Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, India
| | - Sanjeev Waghmare
- Stem Cell Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, India
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Chen Y, Ding X, Bai X, Zhou Z, Liu Y, Zhang X, Yu J, Hu M. The current advances and future directions of PD-1/PD-L1 blockade in head and neck squamous cell carcinoma (HNSCC) in the era of immunotherapy. Int Immunopharmacol 2023; 120:110329. [PMID: 37207445 DOI: 10.1016/j.intimp.2023.110329] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 05/09/2023] [Accepted: 05/09/2023] [Indexed: 05/21/2023]
Abstract
Immune checkpoint inhibitors (ICIs) have previously demonstrated their efficacy and safety in various solid tumors, and with the growing interest in the application of ICIs in head and neck squamous cell carcinoma (HNSCC), various data have been reported. Mechanistically, HNSCC cells express programmed death ligand 1 (PD-L1), which binds to its receptor programmed death 1 (PD-1). Immune escape plays a key role in disease initiation and progression. Studying the abnormal activation of related pathways of PD-1/PD-L1 will help to understand the way of immunotherapy and find the advantageous population of immunotherapy. How to reduce HNSCC-related mortality and morbidity in this process has promoted the search for new therapeutic strategies, especially in the era of immunotherapy. PD-1 inhibitors have demonstrated significant prolongation of survival in recurrent/metastatic (R/M) HNSCC with a favorable safety profile. It also holds great promise in locally advanced (LA) HNSCC, where numerous studies are underway. Although immunotherapy has made great progress in HNSCC research, there are still many challenges. Therefore, in the review, we conducted an in-depth study on the expression of PD-L1 and the regulatory, immunosuppressive mechanisms caused by PD-L1, especially in head and neck squamous cell carcinoma, which is different from other tumors. And further summarize the situation, challenges and development trends of PD-1 and PD-L1 blockade in clinical practice.
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Affiliation(s)
- Yunhao Chen
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong 250117, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
| | - Xingchen Ding
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
| | - Xinbin Bai
- Department of Radiation Oncology, Tumor Hospital of Jining, Jining, Shandong 272007, China
| | - Zihan Zhou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
| | - Yu Liu
- Department of Oncology, Weifang Medical University, Weifang, Shandong 261053, China
| | - Xianbin Zhang
- Department of General Surgery and Integrated Chinese and Western Medicine, Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518060, China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong 250117, China; Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong 250117, China.
| | - Man Hu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
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15
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Li T, Xiang X, Wang Y, Chen C. Association of Elective Neck Dissection With Survival in cT1N0M0 Floor of Mouth Squamous Cell Carcinoma: A Population-Based Propensity Score Matching Analysis. EAR, NOSE & THROAT JOURNAL 2023:1455613231170705. [PMID: 37122112 DOI: 10.1177/01455613231170705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2023] Open
Abstract
BACKGROUND Studies on neck management of early-stage floor of mouth (FOM) squamous cell carcinoma (SCC) are very few and controversial. We aimed to study whether elective neck dissection (END) for patients with clinically stage T1N0M0 (cT1N0M0) FOM SCC is beneficial for survival. METHODS Information on patients diagnosed with cT1N0M0 FOM SCC between 2004 and 2015 was collected from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional risk models and Kaplan-Meier curves were used for survival analysis and log-rank tests were performed to compare whether overall survival (OS) and cancer-specific survival (CSS) differed. Propensity score matching (PSM) was performed to eliminate the effect of confounding variables. RESULTS There were 1014 patients with cT1N0M0 FOM SCC. Among them, END group: 455 cases; observation group: 559 cases. COX regression analysis before PSM demonstrated hazard ratio (HR) in the observation group compared to END (OS: 1.108 (.926-1.326), P = .262; CSS: 1.033 (.772-1.382), P = .827). There was no survival difference between END and observation survival before PSM (5-year OS: 71.8% vs. 67.8%, P = .180; 5-year CSS: 84.5% vs. 84.8%, P = .930); the matched results were the same as before PSM. CONCLUSION Observation may be a more appropriate option compared with END in cT1N0M0 FOM SCC.
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Affiliation(s)
- Tao Li
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China
- Wan Nan Medical College, Wuhu, China
| | - Xianwang Xiang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China
| | - Yi Wang
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China
| | - Chuanjun Chen
- Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China
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16
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Zhang L, Lin S, Zhang Z, Yan C, Liu F. The role of p21-activated kinase 4 in the progression of oral squamous cell carcinoma by targeting PI3K-AKT signaling pathway. Clin Transl Oncol 2023; 25:739-747. [PMID: 36593383 DOI: 10.1007/s12094-022-02980-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/09/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Oral squamous carcinoma (OSCC), the most common head and neck malignancy, has a strong propensity for malignant proliferation and metastasis, which will decrease the survival of patients. P21-activated kinase 4 (PAK4), a classical serine/threonine protein kinase with multiple cellular functions, has an essential role in cancer cell migration and invasion. Here, we elucidated the function and possible molecular mechanisms of the effect of PAK4 on the biological behaviors of OSCC. METHODS The expression of genes and protein was detected by real-time PCR and western blotting. We used oral squamous carcinoma cell lines, Tca8117, Cal 27, SCC 4, and SCC 9 for validation of our cell function data. Flow cytometry, 3D cultures, and clone formation assay were used to detect proliferation of cells. RNA sequencing and bioinformatic analysis was performed to determine the potential function of PAK4. RESULTS Immunohistochemistry, western blotting and real-time PCR demonstrated that PAK4 expression was up-regulated in OSCC tissues. Overexpression of PAK4 promoted the proliferation, migration and invasion of OSCC cell lines. RNA sequencing (RNA-seq) for the transcriptome-wide analysis of differential gene expression followed by bioinformatic analysis was performed to determine the potential function of PAK4. Based on the KEGG enrichment analysis and GO analysis of differential expression genes (DEGs) we found that PAK4 promotes the cell-cycle machinery, which associated with 44 regulated genes, thereby promoting cancer cell differentiation. CONCLUSIONS This study demonstrates that the PAK4 regulates the biological behaviors of OSCC by PI3K-AKT signaling pathway, and these findings might provide a novel strategy for OSCC treatment.
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Affiliation(s)
- Lan Zhang
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China.,Nosocomial Infection Management Office, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, China
| | - Shanfeng Lin
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China
| | - Zeying Zhang
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China.,Department of Endodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China
| | - Cong Yan
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China
| | - Fayu Liu
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, China.
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17
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Effect of Radio-Chemotherapy on PD-L1 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma. J Pers Med 2023; 13:jpm13020363. [PMID: 36836595 PMCID: PMC9965293 DOI: 10.3390/jpm13020363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/14/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
BACKGROUND Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. METHODS A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. RESULTS Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27-0.90). CONCLUSIONS From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression.
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18
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Wang P, Tao L, Yu Y, Wang Q, Ye P, Sun Y, Zhou J. Oral squamous cell carcinoma cell-derived GM-CSF regulates PD-L1 expression in tumor-associated macrophages through the JAK2/STAT3 signaling pathway. Am J Cancer Res 2023; 13:589-601. [PMID: 36895967 PMCID: PMC9989602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 01/26/2023] [Indexed: 03/11/2023] Open
Abstract
Previous study reported that gastric cancer-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) could mediate neutrophil activation and induce PD-L1 expression through JAK2/STAT3 signaling pathway. Moreover, this pathway in various cancers could also regulate PD-L1 expression of tumor cells. Therefore, our study aimed to investigate whether the JAK2/STAT3 pathway regulates PD-L1 expression in tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), which can help us achieve further understanding of immune escape mechanisms in OSCC. We induced human monocytes THP-1 into M0, M1, and M2 macrophages, and applied them to common medium and tumor-conditioned medium, the latter was collected from two types of OSCC cell line. Western blot and RT-PCR were used to detect PD-L1 expression and activation of JAK2/STAT3 pathway in macrophages under various conditions. We found that GM-CSF in tumor-conditioned medium from OSCC cells increased PD-L1 expression in M0 macrophages in a time-dependent manner. Moreover, both GM-CSF neutralizing antibody and JAK2/STAT3 pathway inhibitor AG490 could inhibited its up-regulation. In the meantime, we confirmed that GM-CSF indeed acted through JAK2/STAT3 pathway by measuring phosphorylation of key proteins in this pathway. Therefore, we concluded that OSCC cell-derived GM-CSF was able to up-regulate PD-L1 expression in TAMs through JAK2/STAT3 signaling pathway.
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Affiliation(s)
- Pingping Wang
- Anhui Engineering Research Center for Oral Materials and Application, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China.,Department of Oral Medicine, School of Stomatology, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China
| | - Liqing Tao
- Department of Neurobiology, School of Basic Medical Sciences, Nanjing Medical University Nanjing 211166, Jiangsu, People's Republic of China
| | - Yudu Yu
- Anhui Engineering Research Center for Oral Materials and Application, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China.,Department of Oral Medicine, School of Stomatology, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China
| | - Qiong Wang
- Department of Stomatology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College) Wuhu 241000, Anhui, People's Republic of China.,Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College) Wuhu 241000, Anhui, People's Republic of China
| | - Peihong Ye
- Anhui Engineering Research Center for Oral Materials and Application, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China.,Department of Oral Medicine, School of Stomatology, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China
| | - Yi Sun
- Anhui Engineering Research Center for Oral Materials and Application, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China
| | - Jingping Zhou
- Anhui Engineering Research Center for Oral Materials and Application, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China.,Department of Oral Medicine, School of Stomatology, Wannan Medical College Wuhu 241000, Anhui, People's Republic of China
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Cuevas-González JC, Cuevas-González MV, Espinosa-Cristobal LF, Donohue Cornejo A. Tumor invasion front in oral squamous cell carcinoma. World J Clin Cases 2022; 10:10387-10390. [PMID: 36246821 PMCID: PMC9561579 DOI: 10.12998/wjcc.v10.i28.10387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 08/13/2022] [Accepted: 08/30/2022] [Indexed: 02/05/2023] Open
Abstract
Oral squamous cell carcinoma is a neoplasm that originates from the epithelial mucosa. It is usually more frequent between the fifth and sixth decades of life, and more than 90% of carcinomas of the oral cavity are squamous cell carcinoma. It is an invasive neoplasia with a significant recurrence rate; 40% of patients present with metastases in the cervical lymph nodes at the time of diagnosis. The tumor invasion front is a characteristic of tumor growth, which can be infiltrative or noninvasive. The histopathological parameters examined include the number of mitoses, depth of the tumor, invasion pattern, degree of keratinization, and nuclear pleomorphism. For the pathologist, these parameters are routinely evaluated but are not reported to the treating physician in all cases, which we consider to be useful information when determining the therapeutic route.
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Affiliation(s)
| | - Maria Veronica Cuevas-González
- Faculty of Health Sciences Valle de las Palmas, Universidad Autonoma de Baja California, Tijuana 21480, Baja California, Mexico
| | | | - Alejandro Donohue Cornejo
- Institute of Biomedical Sciences, Universidad Autonoma de Ciudad Juarez, Juarez 32320, Chihuahua, Mexico
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Kitichotkul K, Lertprasertsuke N, Kintarak S, Pongsiriwet S, Powcharoen W, Iamaroon A. Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma. Heliyon 2022; 8:e10667. [PMID: 36212017 PMCID: PMC9535272 DOI: 10.1016/j.heliyon.2022.e10667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 08/09/2022] [Accepted: 09/12/2022] [Indexed: 11/16/2022] Open
Abstract
Objectives Study design Results Conclusion
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Affiliation(s)
- Kit Kitichotkul
- Department of Oral and Maxillofacial, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Nirush Lertprasertsuke
- Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sompid Kintarak
- Department of Stomatology, Faculty of Dentistry, Prince of Songkhla University, Songkhla, Thailand
| | - Surawut Pongsiriwet
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Warit Powcharoen
- Department of Oral and Maxillofacial, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Anak Iamaroon
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
- Excellence Center in Osteology Research and Training Center (ORTC), Chiang Mai University, Chiang Mai, Thailand
- Corresponding author.
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21
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Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems. J Pers Med 2022; 12:jpm12071073. [PMID: 35887569 PMCID: PMC9321150 DOI: 10.3390/jpm12071073] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable.
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