|
1
|
Jamal A, Aldreiwish AD, Banawas SS, Alqurashi YE, Kamal MA, Ahmad F. The paths toward immunotherapy of esophageal cancer: An overview of clinical trials. Int Immunopharmacol 2025; 151:114261. [PMID: 40015204 DOI: 10.1016/j.intimp.2025.114261] [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: 12/30/2024] [Revised: 01/26/2025] [Accepted: 02/06/2025] [Indexed: 03/01/2025]
Abstract
As the seventh-leading contributor to global cancer-related deaths, esophageal cancer (EC) is one of the most challenging types of cancer. Despite advancements in conventional therapies, including surgery, chemotherapy, and radiotherapy, the five-year survival rate remains low, underscoring the need for the development of more efficacious treatment approaches. Immunotherapy has emerged as a promising treatment approach, offering new hope for EC patients. This review provides an in-depth examination of the latest immunotherapeutic strategies for EC, focusing on immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, and oncolytic virotherapy. We critically analyze the current clinical data to highlight the progress and pitfalls of each immunotherapeutic approach for EC. Additionally, we explore the potential for combination therapies, which could overcome the resistance often seen with monotherapies. Finally, we discuss the limitations of current treatments and outline key areas for future research to improve patient outcomes and survival.
Collapse
Affiliation(s)
- Azfar Jamal
- Department of Biology, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia; Health and Basic Science Research Centre, Majmaah University, Al-Majmaah 11952, Saudi Arabia.
| | - Allolo D Aldreiwish
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia
| | - Saeed S Banawas
- Health and Basic Science Research Centre, Majmaah University, Al-Majmaah 11952, Saudi Arabia; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia
| | - Yaser E Alqurashi
- Department of Biology, College of Science Al-Zulfi, Majmaah University, Al-Majmaah 11952, Saudi Arabia
| | - Mohammad Azhar Kamal
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 11942, Saudi Arabia
| | - Fuzail Ahmad
- Respiratory Care Department, College of Applied Sciences, Almaarefa University, Diriya, Riyadh 13713, Saudi Arabia
| |
Collapse
|
|
2
|
Lin Z, Assaraf YG, Kwok HF. Peptides for microbe-induced cancers: latest therapeutic strategies and their advanced technologies. Cancer Metastasis Rev 2024; 43:1315-1336. [PMID: 39008152 DOI: 10.1007/s10555-024-10197-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 06/14/2024] [Indexed: 07/16/2024]
Abstract
Cancer is a significant global health concern associated with multiple distinct factors, including microbial and viral infections. Numerous studies have elucidated the role of microorganisms, such as Helicobacter pylori (H. pylori), as well as viruses for example human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV), in the development of human malignancies. Substantial attention has been focused on the treatment of these microorganism- and virus-associated cancers, with promising outcomes observed in studies employing peptide-based therapies. The current paper provides an overview of microbe- and virus-induced cancers and their underlying molecular mechanisms. We discuss an assortment of peptide-based therapies which are currently being developed, including tumor-targeting peptides and microbial/viral peptide-based vaccines. We describe the major technological advancements that have been made in the design, screening, and delivery of peptides as anticancer agents. The primary focus of the current review is to provide insight into the latest research and development in this field and to provide a realistic glimpse into the future of peptide-based therapies for microbe- and virus-induced neoplasms.
Collapse
Affiliation(s)
- Ziqi Lin
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR
- Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR
| | - Yehuda G Assaraf
- The Fred Wyszkowski Cancer Research Lab, Faculty of Biology, Technion-Israel Instituteof Technology, Haifa, 3200003, Israel
| | - Hang Fai Kwok
- Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR.
- Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR.
- MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
| |
Collapse
|
|
3
|
Makino T, Miyata H, Yasuda T, Kitagawa Y, Muro K, Park JH, Hikichi T, Hasegawa T, Igarashi K, Iguchi M, Masaoka Y, Yano M, Doki Y. A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma. Esophagus 2024; 21:447-455. [PMID: 38990441 PMCID: PMC11405444 DOI: 10.1007/s10388-024-01072-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/02/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. RESULTS A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. CONCLUSIONS S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.
Collapse
Affiliation(s)
- Tomoki Makino
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takushi Yasuda
- Department of Surgery, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan
| | - Jae-Hyun Park
- OncoTherapy Science, Inc., Kawasaki, Kanagawa, Japan
| | - Tetsuro Hikichi
- Laboratory Department, Cancer Precision Medicine, Inc., Kawasaki, Kanagawa, Japan
| | | | | | - Motofumi Iguchi
- Medical Affairs Department, Shionogi & Co., Ltd, Osaka, Japan
| | | | - Masahiko Yano
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
- Kyowakai Hospital, Osaka, Japan
| | - Yuichiro Doki
- Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| |
Collapse
|
|
4
|
Zhao YX, Zhao HP, Zhao MY, Yu Y, Qi X, Wang JH, Lv J. Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:2638-2656. [PMID: 38855150 PMCID: PMC11154680 DOI: 10.3748/wjg.v30.i20.2638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/26/2024] [Accepted: 05/13/2024] [Indexed: 05/27/2024] Open
Abstract
As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.
Collapse
Affiliation(s)
- Yi-Xin Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - He-Ping Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Meng-Yao Zhao
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Yan Yu
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Xi Qi
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| | - Ji-Han Wang
- Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, Shaanxi Province, China
| | - Jing Lv
- Department of Clinical Laboratory, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, Shaanxi Province, China
| |
Collapse
|
|
5
|
Wang H, Xu Y, Zuo F, Liu J, Yang J. Immune-based combination therapy for esophageal cancer. Front Immunol 2022; 13:1020290. [PMID: 36591219 PMCID: PMC9797857 DOI: 10.3389/fimmu.2022.1020290] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Esophageal cancer (EC) is an aggressive malignancy raising a healthcare concern worldwide. Standard treatment options include surgical resection, chemotherapy, radiation therapy, and targeted molecular therapy. The five-year survival rate for all stages of EC is approximately 20%, ranging from 5% to 47%, with a high recurrence rate and poor prognosis after treatment. Immunotherapy has shown better efficacy and tolerance than conventional therapies for several malignancies. Immunotherapy of EC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, has shown clinical advantages. In particular, monoclonal antibodies against PD-1 have a satisfactory role in combination therapy and are recommended for first- or second-line treatments. Here, we present a systematic summary and analysis of immunotherapy-based combination therapies for EC.
Collapse
Affiliation(s)
- Huiling Wang
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Yufei Xu
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Fengli Zuo
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China
| | - Junzhi Liu
- West China School of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Jiqiao Yang
- Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China,Breast Center, West China Hospital of Sichuan University, Chengdu, China,*Correspondence: Jiqiao Yang,
| |
Collapse
|
|
6
|
Shimizu N, Hussain SA, Obara W, Yamasaki T, Takashima S, Hasegawa T, Iguchi M, Igarashi K, Ogawa O, Fujioka T. A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma. Bladder Cancer 2022; 8:179-192. [PMID: 38993370 PMCID: PMC11181746 DOI: 10.3233/blc-211592] [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: 08/03/2021] [Accepted: 04/06/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy. OBJECTIVE To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC. MATERIALS AND METHODS This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks. RESULTS The CTL induction rate in the S-588410 group was 93.3% (p < 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1-3) reported in 93.3% (n = 42/45) of participants. CONCLUSIONS S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22).
Collapse
Affiliation(s)
- Nobuaki Shimizu
- Department of Urology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
| | | | - Wataru Obara
- Department of Urology, Iwate Medical University, Morioka, Iwate, Japan
| | - Toshinari Yamasaki
- Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | | | | | | | | | - Osamu Ogawa
- Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tomoaki Fujioka
- Department of Urology, Iwate Medical University, Morioka, Iwate, Japan
| |
Collapse
|
|
7
|
Wolf SP, Wen FT, Schreiber H. Criteria to make animal studies more relevant to treating human cancer. Curr Opin Immunol 2022; 74:25-31. [PMID: 34619458 PMCID: PMC8901458 DOI: 10.1016/j.coi.2021.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/28/2021] [Accepted: 09/11/2021] [Indexed: 02/03/2023]
Abstract
Certain aspects of experimental tumor models in mice most accurately reflect the biology and immunology of cancer in patients. A survey of experimental cancer immunotherapy papers published in 2020 shows most do not achieve cancer shrinkage although treatment is initiated at an early time point after cancer cell injection, which does not reflect cancer immunotherapy in patients. Even then, few current experimental approaches eradicate the injected malignant cells, most only delay outgrowth. The value of targeting mutation-encoded tumor-specific antigens becomes increasingly evident while problems of finding normal gene-encoded tumor-associated antigens as safe, effective targets persist. It might be time to refocus on realistic experimental settings and truly cancer-specific targets. These antigens are associated with the least risk of side effects.
Collapse
Affiliation(s)
- Steven P Wolf
- Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA; David and Etta Jonas Center for Cellular Therapy, The University of Chicago, Chicago, IL, 60637, USA
| | - Frank T Wen
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Hans Schreiber
- Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA; David and Etta Jonas Center for Cellular Therapy, The University of Chicago, Chicago, IL, 60637, USA; Committee on Cancer Biology and Committee on Immunology, The University of Chicago, Chicago, IL, 60637, USA.
| |
Collapse
|
|
8
|
Immunotherapy for Esophageal Cancer: State-of-the Art in 2021. Cancers (Basel) 2022; 14:cancers14030554. [PMID: 35158822 PMCID: PMC8833794 DOI: 10.3390/cancers14030554] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/19/2022] [Accepted: 01/20/2022] [Indexed: 02/01/2023] Open
Abstract
The management of esophageal cancer (EC) has experienced manifold changes during the last decades. Centralization of EC treatment has been introduced in many countries, subsequently allowing the development of specialized high-volume centers. Minimal invasive surgery has replaced open surgery in many centers, whereas more potent systemic treatments have been introduced in clinical practice. Newer chemotherapy regimens increase long-term survival. Nevertheless, the overall survival of EC patients remains dismal for advanced tumor stages. In this direction, a wide range of targeted biologic agents (immunotherapy) is currently under assessment. Anti- Human Epidermal Growth Factor Receptor-2 (HER-2) monoclonal antibodies are used in HER2 (+) tumors, predominantly well-differentiated adenocarcinomas, and are currently assessed in the neoadjuvant setting (TRAP, INNOVATION trials). Immune checkpoint inhibitors Nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181), have demonstrated a survival benefit compared with conventional chemotherapy in heavily pre-treated progressive disease. More recently, CheckMate-577 showed very promising results for nivolumab in a curative adjuvant setting, improving disease-free survival mainly for esophageal squamous cell carcinoma. Several ongoing trials are investigating novel targeted agents in the preoperative setting of locally advanced EC. In addition, other immunomodulatory approaches such as peptide vaccines and tumor infiltrating lymphocytes (TILs) are currently under development and should be increasingly integrated into clinical practice.
Collapse
|
|
9
|
Cui Y, Hou R, Lv X, Wang F, Yu Z, Cui Y. Identification of Immune-Cell-Related Prognostic Biomarkers of Esophageal Squamous Cell Carcinoma Based on Tumor Microenvironment. Front Oncol 2021; 11:771749. [PMID: 34760708 PMCID: PMC8573319 DOI: 10.3389/fonc.2021.771749] [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: 09/07/2021] [Accepted: 10/04/2021] [Indexed: 11/13/2022] Open
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers in the world. The 5-year survival rate of ESCC is <30%. However, few biomarkers can accurately predict the prognosis of patients with ESCC. We aimed to identify potential survival-associated biomarkers for ESCC to improve its poor prognosis. Methods ImmuneAI analysis was first used to access the immune cell abundance of ESCC. Then, ESTIMATE analysis was performed to explore the tumor microenvironment (TME), and differential analysis was used for the selection of immune-related differentially expressed genes (DEGs). Weighted gene coexpression network analysis (WGCNA) was used for selecting the candidate DEGs. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to build the immune-cell-associated prognostic model (ICPM). Kaplan–Meier curve of survival analysis was performed to evaluate the efficacy of the ICPM. Results Based on the ESTIMATE and ImmuneAI analysis, we obtained 24 immune cells’ abundance. Next, we identified six coexpression module that was associated with the abundance. Then, LASSO regression models were constructed by selecting the genes in the module that is most relevant to immune cells. Two test dataset was used to testify the model, and we finally, obtained a seven-genes survival model that performed an excellent prognostic efficacy. Conclusion In the current study, we filtered seven key genes that may be potential prognostic biomarkers of ESCC, and they may be used as new factors to improve the prognosis of cancer.
Collapse
Affiliation(s)
- Yiyao Cui
- Department of Thoracic Surgery, Beijing Friendship Hospital, Affiliated to the Capital University of Medical Sciences, Beijing, China
| | - Ruiqin Hou
- Department of Blood Transfusion, Peking University People's Hospital, Beijing, China
| | - Xiaoshuo Lv
- Department of Thoracic Surgery, Beijing Friendship Hospital, Affiliated to the Capital University of Medical Sciences, Beijing, China
| | - Feng Wang
- Department of Thoracic Surgery, Beijing Friendship Hospital, Affiliated to the Capital University of Medical Sciences, Beijing, China
| | - Zhaoyan Yu
- Department of Otorhinolaryngology, Shandong Public Health Clinical Center, Jinan, China
| | - Yong Cui
- Department of Thoracic Surgery, Beijing Friendship Hospital, Affiliated to the Capital University of Medical Sciences, Beijing, China
| |
Collapse
|
|
10
|
Immunogenomics in personalized cancer treatments. J Hum Genet 2021; 66:901-907. [PMID: 34193979 DOI: 10.1038/s10038-021-00950-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/29/2021] [Accepted: 06/09/2021] [Indexed: 12/30/2022]
Abstract
Recent advances in next-generation sequencing technologies have led to significant improvements in cancer genomic research and cancer treatment. Through the use of comprehensive cancer genome data, precision medicine has become more of a reality; albeit, at present, only ~10-15% of patients can benefit from current genomic testing practices. Improvements in cancer genome analyses have contributed to a better understanding of antitumor immunity and have provided solutions for targeting highly cancer-specific neoantigens generated from somatic mutations in individual patients. Since then, numerous studies have demonstrated the importance of neoantigens and neoantigen-reactive T cells in the tumor microenvironment and how their presence influences the beneficial responses associated with various cancer immunotherapies, including immune checkpoint inhibitor therapy. Indeed, cancer immunotherapies that explicitly target neoantigens specific to individual cancer patients would lead to the ultimate form of cancer precision medicine. For this to be realized, several issues would need to be overcome, including the accurate prediction and selection of neoantigens that can induce cytotoxic T cells in individual patients. The precise prediction of target neoantigens will likely accelerate the development of personalized immunotherapy including cancer vaccines and T-cell receptor-engineered T-cell therapy for patients with cancer.
Collapse
|
|
11
|
Yu J, Wang Q, Zhang X, Guo Z, Cui X. Mechanisms of Neoantigen-Targeted Induction of Pyroptosis and Ferroptosis: From Basic Research to Clinical Applications. Front Oncol 2021; 11:685377. [PMID: 34123855 PMCID: PMC8191503 DOI: 10.3389/fonc.2021.685377] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/06/2021] [Indexed: 12/14/2022] Open
Abstract
Neoantigens are tumor-specific antigens (TSAs) that are only expressed in tumor cells. They are ideal targets enabling T cells to recognize tumor cells and stimulate a potent antitumor immune response. Pyroptosis and ferroptosis are newly discovered types of programmed cell death (PCD) that are different from apoptosis, cell necrosis, and autophagy. Studies of ferroptosis and pyroptosis of cancer cells are increasing, and strategies to modify the tumor microenvironment (TME) through ferroptosis to inhibit the occurrence and development of cancer, improve prognosis, and increase the survival rate are popular research topics. In addition, adoptive T cell therapy (ACT), including chimeric antigen receptor T cell (CAR-T) technology and T cell receptor engineered T cell (TCR-T) technology, and checkpoint blocking tumor immunotherapies (such as anti-PD- 1 and anti-PD-L1 agents), tumor vaccines and other therapeutic technologies that rely on tumor neoantigens are rapidly being developed. In this article, the relationship between neoantigens and pyroptosis and ferroptosis as well as the clinical role of neoantigens is reviewed.
Collapse
Affiliation(s)
- Jie Yu
- School of Basic Medicine Sciences, Weifang Medical University, Weifang, China
| | - Qing Wang
- School of Basic Medicine Sciences, Weifang Medical University, Weifang, China
| | - Xiaoyun Zhang
- School of Basic Medicine Sciences, Weifang Medical University, Weifang, China
| | - Zhiliang Guo
- The Department of Spine Surgery, The 80th Group Army Hospital of Chinese People's Liberation Army (PLA) of China, Weifang, China
| | - Xiaodong Cui
- School of Basic Medicine Sciences, Weifang Medical University, Weifang, China
| |
Collapse
|
|
12
|
Lonie JM, Barbour AP, Dolcetti R. Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches. Cancer Treat Rev 2021; 98:102219. [PMID: 33993033 DOI: 10.1016/j.ctrv.2021.102219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/30/2021] [Accepted: 05/05/2021] [Indexed: 12/12/2022]
Abstract
With an incidence that is constantly rising, oesophageal adenocarcinoma (OAC) is becoming an increasing health burden worldwide. Although significant advances in treatment regimens have improved patient outcomes, survival rates for this deadly cancer remain unsatisfactory. This highlights the need to improve current therapeutic approaches and develop novel therapeutic strategies for treating OAC patients. The advent of immunotherapy has revolutionised treatment across a range of malignancies, however outcomes in OAC show modest results. The inherent resistance of OAC to treatment reflects the complex genomic landscape of this cancer, which displays a lack of ubiquitous driver mutations and large-scale genomic alterations along with high tumour and immune heterogeneity. Research into the immune landscape of OAC is limited, and elucidation of the mechanisms surrounding the immune responses to this complex cancer will result in improved therapeutic approaches. This review explores what is known about the immuno-biology of OAC and explores promising therapeutic avenues that may improve responses to immunotherapeutic regimens.
Collapse
Affiliation(s)
- James M Lonie
- The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
| | - Andrew P Barbour
- The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia; Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Riccardo Dolcetti
- The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia; Sir Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|
|
13
|
Kaida H, Kitajima K, Nakajo M, Ishibashi M, Matsunaga T, Minamimoto R, Hirata K, Nakatani K, Hung A, Hattori S, Yasuda T, Ishii K. Predicting tumor response and prognosis to neoadjuvant chemotherapy in esophageal squamous cell carcinoma patients using PERCIST: a multicenter study in Japan. Eur J Nucl Med Mol Imaging 2021; 48:3666-3682. [PMID: 33934168 DOI: 10.1007/s00259-021-05365-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 04/11/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE To investigate the usefulness of the positron emission tomography response criteria in solid tumors 1.0 (PERCIST1.0) for predicting tumor response to neoadjuvant chemotherapy and prognosis and determine whether PERCIST improvements are necessary for esophageal squamous cell carcinoma (ESCC) patients. PATIENTS AND METHODS We analyzed the cases of 177 ESCC patients and examined the association between PERCIST and their pathological responses. Associations of whole-PERCIST with progression-free survival (PFS) and overall survival (OS) were evaluated by a Kaplan-Meier analysis and Cox proportional hazards model. To investigate potential PERCIST improvements, we used the survival tree technique to understand patients' prognoses. RESULTS There were significant correlations between the pathologic response and PERCIST of primary tumor (p < 0.001). The optimal cutoff value of the primary tumors' SULpeak response to classify pathologic responses was -50.0%. The diagnostic accuracy of SULpeak response was 87.3% sensitivity, 54.1% specificity, 68.9% accuracy, positive predictive value 60.5%, and negative predictive value 84.1%. Whole-PERCIST was significantly associated with PFS and OS. The survival tree results indicated that a high reduction of the whole SULpeak response was significantly correlated with the patients' prognoses. The cutoff values for the separation of prognoses were - 52.5 for PFS and - 47.1% for OS. CONCLUSION PERCIST1.0 can help predict tumor responses and prognoses. However, 18F-FDG-PET/CT tends to underestimate residual tumors in histopathological response evaluations. Modified PERCIST, in which the partial metabolic response is further classified by the SULpeak response (-50%), might be more appropriate than PERCIST1.0 for evaluating tumor responses and stratifying high-risk patients for recurrence and poor prognosis.
Collapse
Affiliation(s)
- Hayato Kaida
- Department of Radiology, Kindai University Faculty of Medicine, 377-2, Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan.
| | - Kazuhiro Kitajima
- Department of Radiology, Division of Nuclear Medicine and PET Center, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Masatoyo Nakajo
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-5-31, Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Mana Ishibashi
- Division of Radiology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, 36-1, Nishi-cho, Yonago, Tottori, 683-8504, Japan
| | - Tomoyuki Matsunaga
- Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Tottori University of Faculty of Medicine, 36-1, Nishi-cho, Yonago, Tottori, 683-8504, Japan
| | - Ryogo Minamimoto
- Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Kenji Hirata
- Department of Diagnostic Imaging, Hokkaido University Graduate School of Medicine, Kita15, Nishi 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Koya Nakatani
- Department of Diagnostic Radiology, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Ao Hung
- Department of Biomedical Statistics, Osaka University Graduate School of Medicine, 2-2, Yamadagaoka, Suita, Osaka, 565-0871, Japan
| | - Satoshi Hattori
- Department of Biomedical Statistics, Osaka University Graduate School of Medicine, 2-2, Yamadagaoka, Suita, Osaka, 565-0871, Japan.,Institute for Open and Transdisciplinary Research Initiative, Osaka University, 2-2, Yamadagaoka, Suita, Osaka, 565-0871, Japan
| | - Takushi Yasuda
- Department of Surgery, Kindai University Faculty of Medicine, 377-2, Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan
| | - Kazunari Ishii
- Department of Radiology, Kindai University Faculty of Medicine, 377-2, Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan
| |
Collapse
|