Heat shock proteins have been implicated in the process of carcinogenesis. HSPA14, a member of the heat shock protein family, remains poorly understood in terms of its significance and pathomechanisms in breast cancer.

We analyzed the expression levels of HSPA14 and its prognostic significance in breast cancer using TCGA data. TCGA data was used to investigate the association between HSPA14 expression and clinicopathological features in breast cancer patients. GSEA analysis was conducted to identify the biological function of HSPA14. Spearman's correlation analysis was performed to examine the correlation between HSPA14 expression and immune cell infiltration, as well as immune checkpoint genes. Single cell transcriptomic data from GSE114727 was utilized to calculate the expression of HSPA14 in different cell subpopulations. The data on HSPA14 levels and drug sensitivity were extracted from the CellMiner dataset. The mRNA expression of HSPA14 was validated through cell experiments.

HSPA14 expression is elevated in breast cancer, which is associated with poor overall survival. It can serve as a diagnostic biomarker for breast cancer patients. Pathway analysis revealed that HSPA14-associated differential genes are involved in cell cycle, apoptosis, cellular response to heat stress, and more. Additionally, HSPA14 expression is significantly correlated with the immune microenvironment. The expression of HSPA14 may also indicate drug sensitivity.

Our study elucidates the involvement of HSPA14 in tumorigenesis, particularly in modulating the immune response, shaping the immune microenvironment, and contributing to drug resistance, which are pivotal for the development of personalized breast cancer therapies.

The tumor microenvironment (TME) represents a heterogeneous, complicated ecosystem characterized by intricate interactions between tumor cells and immune cells. During the past decade, immune cells especially T cells were found to play an important role in the progression of tumor and many related immune checkpoints drugs were created. In recent years, more and more scientists revealed the critical role of B-cells within the TME, particularly various populations of non-malignant B cells. Some studies indicated that non-malignant B cells may exert a 'double-edged sword' role in solid tumors. However, there has been comparatively less focus on the role of non-malignant B cells in hematologic malignancies. In this review, we characterized the development of B cells and summarized its functions of antitumor immunity within TME, with an emphasis on elucidating the roles and potential mechanisms of non-malignant B cells in the progression of hematologic diseases including classical Hodgkin's lymphoma, non-Hodgkin's B-cell lymphoma, non-Hodgkin's T-cell lymphoma, leukemia and multiple myeloma.

Membrane-associated RING-CH8 (MARCH8) is a member of the recently discovered MARCH family of ubiquitin ligases. MARCH8 has been shown to participate in immune responses. However, the role of MARCH8 in prognosis and immunology in human cancers remains largely unknown. The expression of MARCH8 protein was detected via immunohistochemistry in non-small cell lung cancer (NSCLC) and non-cancerous lung tissues. The study investigated the role of MARCH8 in tumor immunity through pan-cancer analysis of multiple databases. MARCH8 genetic alternations and expression were explored with the cBioPortal, GTEx, and TCGA databases. We investigated the role of MARCH8 expression in clinical relevance, prognosis, tumor immune microenvironment, immune checkpoint (ICP) with a series of bioinformatics tools and methods, such as TISIDB database, ESTIMATE, and CIBERSORT method. MARCH8 expression showed cancer-specific dysregulation and was associated with the prognosis of patients in various cancers. MARCH8 was related to the tumor microenvironment and participated in tumor immune regulation. Furthermore, low expression of MARCH8 was associated with poor prognosis and might serve as an independent prognostic biomarker for NSCLC patients. The comprehensive pan-cancer analysis revealed the potential of MARCH8 in tumor-targeted therapy, and suggested MARCH8 as a promising prognostic and immunological pan-cancer biomarker.

Non-small cell lung cancer (NSCLC) has shown limited response to immunotherapy, primarily due to an immunosuppressive tumor microenvironment characterized by hypoxia and lipid raft formation, which together inhibit T-cell infiltration and function, impeding effective immune responses. To address these challenges, we developed Abstatin, an albumin-bound fluvastatin formulation that targets lipid raft disruption and mitochondrial respiration inhibition, aiming to reduce hypoxia and destabilize lipid rafts to enhance T-cell activity within the tumor. Using bioinformatics analysis, in vitro assays, and in vivo studies in both murine and humanized PDX models, we demonstrated that Abstatin reprograms the NSCLC microenvironment by concurrently lowering hypoxia levels and lipid raft integrity, thereby restoring T-cell infiltration, enhancing cytotoxic T-cell function, and ultimately improving response to Anti-PD-1 therapy. Results showed that Abstatin significantly amplifies Anti-PD-1 efficacy with minimal toxicity, indicating a favorable safety profile for clinical use. This study highlights Abstatin as a promising immunotherapy adjuvant that addresses critical barriers in NSCLC by modulating metabolic pathways linked to immune resistance. Abstatin's approach, which combines modulation of cellular metabolism with immune sensitization, broadens the potential of immunotherapy and provides a practical, scalable strategy to enhance treatment outcomes in NSCLC and potentially other tumors, offering insights into combinatory cancer therapies.

Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.

Nanocatalytic platforms are promising in cancer therapeutics via combining multiple treatments, which can be leveraged through the metabolic dysfunction in cancer progression. However, the lack of effective tumor delivery platforms hampers this approach. Here, a gelatin-based platform is designed that is preloaded with gold nanoparticles and photothermal polypyrrole (GNPs@AuNPs-PPy) with an acid-induced doping enhancement. Benefiting from the tumor associated overexpression of H2O2, peroxidase-like Au nanoparticles induce a burst of oxidative reactive oxygen species in the local tumor microenvironment (TME). Subsequent orchestration of redox surroundings recruits immune cells, showcasing an effective antineoplastic pathway. Under near infrared light (NIR) irradiation, nanohybrids exhibit dual pH/NIR enhanced drug release within the TME, while allowing for multimodal imaging-guided theranostics. Leveraging this modality, GNPs@AuNPs-PPy delivers quercetin (a natural antitumor mediator) in TME, boosting anti-tumor therapy. The gelatin-mediated nanomedicine provides an alternative platform for combinatorial dynamic antitumor treatment.

Conventional dendritic cell and plasmacytoid dendritic cell (pDC) subsets have specialized functions that can be modulated by the tumor microenvironment, and produce different interferons that are central to antitumor immune responses. While the function of type I interferons in tumor immunity is well characterized, that of type III interferons produced by type 1 conventional dendritic cells in the tumor microenvironment remains unclear. Here we demonstrate in vitro that type III interferons orchestrate pDC survival, activation and TLR7 expression in the blood, thereby enhancing pDC responses to a TLR7 ligand. Moreover, we show that tumor-associated pDCs express the highest level of IFNLR1, and that these immune cell subsets are the most responsive to IFN-III. Importantly, type III interferons prevent the inhibition of pDCs induced by TGF-β or PGE2 in tumor soluble milieu from patients to restores production of IFN-α in pDCs. With TGF-β or PGE2 having pleotropic functions in immune regulation, our results thus implicate IFN-III-mediated immune modulation to have broad impact on various pathological situations.

Neuronal signals have emerged as pivotal regulators of B cells that regulate antitumor immunity and tumor progression. However, the functional relevance and mechanistic basis of the effects of the neurotransmitter dopamine (DA) on tumor immunity remain elusive. Here, we discovered that plasma DA levels are positively correlated with circulating B cell numbers and potently activate B cell responses in a manner dependent on the DRD5 receptor. Notably, DRD5 signaling enhanced the Janus kinase 1 (JAK1)-STAT1 signaling in B cell responses, which enhanced B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion and cytotoxicity in tumor-specific effector of T cells. Our findings demonstrate that DA signaling suppresses tumor progression and highlight DRD5 as a promising target for cancer immunotherapy.

Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, primary resistance and acquired resistance continue to limit their efficacy for many patients. To address resistance and enhance the anti-tumor activity within the tumor immune microenvironment (TIME), numerous therapeutic strategies targeting both innate and adaptive immune cells have emerged. These include combination therapies with ICIs, chimeric antigen receptor T-cell (CAR-T), chimeric antigen receptor macrophages (CAR-Ms) or chimeric antigen receptor natural killer cell (CAR-NK) therapy, colony stimulating factor 1 receptor (CSF1R) inhibitors, dendritic cell (DC) vaccines, toll-like receptor (TLR) agonists, cytokine therapies, and chemokine inhibition. These approaches underscore the significant potential of the TIME in cancer treatment. This article provides a comprehensive and up-to-date review of the mechanisms of action of various innate and adaptive immune cells within the TIME, as well as the therapeutic strategies targeting each immune cell type, aiming to deepen the understanding of their therapeutic potential.

Immune cells within the tumor microenvironment impact cancer progression, resistance, response to treatments. Despite remarkable outcomes for some cancer patients, immunotherapies remain unsatisfactory for others. Here, we designed an experimental setting using the Alb-R26 Met "inside-out" mouse model, faithfully recapitulating molecular features of liver cancer patients, to explore the effects of distinct anticancer targeted therapies on the tumor immune landscape. Using two treatments in clinical trials for different cancer types, Decitabine and MEK+BCL-XL blockage, we show their capability to trigger tumor regression in Alb-R26 Met mice and to superimpose distinct profiles of immune cell types and immune-checkpoints, impacting immunotherapy response. A machine learning approach processing tumor imaging and immune profile data identified a putative signature predicting tumor treatment response in mice and patients. Outcomes exemplify how the tumor immune microenvironment is differentially reshaped by distinct anticancer agents and highlight the importance of measuring its modulation during treatment to optimize oncotherapy and immunotherapy combinations.

Prostate cancer (PCa) continues to pose substantial clinical challenges, with molecular heterogeneity significantly impacting therapeutic decision-making and disease trajectories. Emerging evidence implicates protein lactylation-a novel epigenetic regulatory mechanism-in oncogenic processes, though its prognostic relevance in PCa remains underexplored. Through integrative bioinformatics interrogation of lactylation-associated molecular signatures, we established prognostic correlations using multivariable feature selection methodologies. Initial screening via differential expression analysis (limma package) coupled with Cox proportional hazards modeling revealed 11 survival-favorable regulators and 16 hazard-associated elements significantly linked to biochemical recurrence. To enhance predictive precision, ensemble machine learning frameworks were implemented, culminating in a 10-gene lactylation signature demonstrating robust discriminative capacity (concordance index = 0.738) across both primary (TCGA-PRAD) and external validation cohorts (DKFZ). Multivariable regression confirmed the lactylation score's prognostic independence, exhibiting prominent associations with clinicopathological parameters including tumor staging and metastatic potential. The developed clinical-molecular nomogram achieved superior predictive accuracy (C - index > 0.7) through the synergistic integration of biological and clinical covariates. Tumor microenvironment deconvolution uncovered distinct immunological landscapes, with high-risk stratification correlating with enriched stromal infiltration and immunosuppressive phenotypes. Pathway enrichment analyses implicated chromatin remodeling processes and cytokine-mediated inflammatory cascades as potential mechanistic drivers of prognostic divergence. Therapeutic vulnerability profiling demonstrated differential response patterns: low-risk patients exhibited enhanced immune checkpoint inhibitor responsiveness, whereas high-risk subgroups showed selective chemosensitivity to docetaxel and mitoxantrone. Functional validation in PC-3 models revealed AK5 silencing induced proapoptotic effects, suppressed metastatic potential of migration and invasion, and modulated immune checkpoint regulation through CD276 coexpression. These multimodal findings position lactylation dynamics, particularly AK5-mediated pathways, as promising therapeutic targets and stratification biomarkers in PCa management.

With the rise of immunotherapy, the treatment approach for non-small cell lung cancer (NSCLC) has undergone revolutionary changes. However, the prognosis for NSCLC patients has not been significantly improved due to the development of acquired drug resistance. Therefore, there is an urgent need to develop new and more effective drugs for treating NSCLC or improving tumor treatment resistance. Traditional Chinese medicine (TCM) has been gradually incorporated into the combined treatment of NSCLC. Its active components (also known as natural products) exhibit novel structures, multi-target effects, diverse pathways, minimal toxicity, and varied biological activities, which play a therapeutic role in various diseases. Thus, natural products hold great potential for future clinical applications.

Screening main traditional plants widely used in NSCLC and their derived natural products, as well as exploring the mechanisms by which these natural products act on NSCLC-particularly focusing on their applications-can provide valuable insights for the development of therapeutic drugs targeting NSCLC.

A comprehensive, computerized literature search was conducted in PubMed, Embase, Web of Science, Cochrane Library, CNKI Scholar, the American Chemical Abstracts, and Wanfang Database up to June 2024, using the following keywords: "traditional Chinese medicine", "herbal medicine", "medicinal plants", and "herbal", paired with terms such as "non-small cell lung cancer", "therapy", "natural products", and "active ingredient".

Summarizing current research findings, we discovered eleven medicinal plants containing a total of fourteen natural products. Natural products have a significant impact on tumor progression in NSCLC, including apotosis, autophagy, pyrotosis, cell-cycle arrest and metasis. Moreover, natural products can modulate the activities of various immune cells and reshape the immune microenvironment. Combined with conventional cancer treatments, natural products demonstrate promising therapeutic effects and effectively reverse drug resistance. Furthermore,the use of nano-drug delivery systems to address limitations associated with natural products.

This review summarizes eleven medicinal plants containing a total of fourteen natural products that can enhance NSCLC treatment and indicates their action mechanisms. Furthermore, we also discuss limitations of natural products and explore the use of nano-drug delivery systems to address limitations associated with natural products.

Natural killer cell-derived exosomes (NK-Exos) hold great promise as immune modulators and immunotherapeutics against cancer due to their intrinsically latent anti-tumor effects. They use these nanosized vesicles to deliver cytotoxic molecules, such as perforin, granzymes, and miRNAs, directly to cancer cells to kill them, avoiding immune suppression. NK-Exos has particular efficacy for treating aggressive breast cancer by modulating the TME to activate the immune response and suppress immunosuppressive factors. Bioengineering advances have extended the therapeutic potential of NK-Exos, which permits precise tumor cell targeting and efficient delivery of therapeutic payloads, including small RNAs and chemotherapeutic agents. In engineered NK-Exos, sensitization of cancer cells to apoptosis, reduction of tumor growth, and resistance to drugs have been demonstrated to be highly effective. When combined, NK-Exos synergizes with radiotherapy, chemotherapy, or checkpoint inhibitors, enhancing therapeutic efficacy, and minimizing systemic toxicity. This review emphasizes the critical role of NK-Exos in breast cancer treatment, their integration into combination therapies, and the need for further research to overcome existing limitations and fully realize their clinical potential.

Bioadhesives have found significant use in medicine and engineering, particularly for wound care, tissue engineering, and surgical applications. Compared to traditional wound closure methods such as sutures and staples, bioadhesives offer advantages, including reduced tissue damage, enhanced healing, and ease of implementation. Recent progress highlights the synergy of bioadhesives and immunoengineering strategies, leading to immunomodulatory bioadhesives capable of modulating immune responses at local sites where bioadhesives are applied. They foster favorable therapeutic outcomes such as reduced inflammation in wounds and implants or enhanced local immune responses to improve cancer therapy efficacy. The dual functionalities of bioadhesion and immunomodulation benefit wound management, tissue regeneration, implantable medical devices, and post-surgical cancer management. This review delves into the interplay between bioadhesion and immunomodulation, highlighting the mechanobiological coupling involved. Key areas of focus include the modulation of immune responses through chemical and physical strategies, as well as the application of these bioadhesives in wound healing and cancer treatment. Discussed are remaining challenges such as achieving long-term stability and effectiveness, necessitating further research to fully harness the clinical potential of immunomodulatory bioadhesives.

Skin cutaneous melanoma represents a significant threat among skin cancers. Investigating key methylated genes with prognostic implications remains an area ripe for exploration in this field. This study aims to identify survival-associated methylated genes and their specific methylation sites in skin cutaneous melanoma through integrated bioinformatic analysis. Utilizing data from the Cancer Genome Atlas database, gene methylation and expression files were analyzed. The results indicate that patients with skin cutaneous melanoma exhibiting high expression of hypomethylated HHEX experience better outcomes compared to those with low expression of hypermethylated HHEX. Furthermore, fifteen methylation sites within HHEX were found to significantly correlate with its expression levels. Expression of HHEX demonstrated a downward trend across pathological stages I-IV. The identified driven gene, HHEX, likely plays a crucial role in the survival of skin cutaneous melanoma patients. These findings provide new epigenetic insights and potential targets for early prognosis prediction in skin cutaneous melanoma.

Although lymphopenia is linked to immune suppression favoring tumor growth, the effect of different radiation types on specific T-lymphocyte subsets remains unclear. Among the T-lymphocyte subpopulations, CD8+-lymphocytes serve as key effectors in cancer immunity. This study aimed to examine the changes in T-lymphocyte subpopulations in both tumor-free and glioblastoma-bearing mice following brain-irradiation.

The study was divided into two main phases. First, C57BL/6 mice, with or without glioblastoma (GL261 cells), received hemispheric brain-irradiation or no-treatment. T-lymphocyte subpopulations were analyzed using flow cytometry at various timepoint. The effect of tumor size and brain-irradiation on these cells was assessed using correlation analysis. Next, C57BL/6 mice were subjected to different brain-irradiation conditions. Blood samples were collected during and post-irradiation to analyze T-lymphocyte subpopulations, and tree-based modeling was used to determine radiation parameters impact on naïve CD8+-lymphocyte levels.

Glioblastoma reduced all T-lymphocyte subpopulations by day 15 post-inoculation. Radiotherapy decreased regulatory and effector CD4+-lymphocytes in both tumor-free and glioblastoma-bearing mice, but not naïve or memory CD4+-lymphocytes, in both tumor-free and glioblastoma-bearing mice. In tumor-free mice, radiotherapy had no effect on CD8+-lymphocytes, but reduced all CD8+-lymphocyte types in glioblastoma-bearing mice. Glioblastoma size negatively affected CD8+-lymphocytes. Brain-irradiation persistently reduced naïve and memory CD8+-lymphocytes, but effector and regulatory T-lymphocytes recovered. Exposure of lymph nodes to radiation worsened CD8+-lymphocyte reduction.

These findings confirm that the presence of glioblastoma and brain-irradiation affect T-lymphocyte subpopulations in mice. The inclusion of lymph nodes in the irradiated area led to a long-term decrease in naïve CD8+-lymphocytes. Further mechanistic studies are needed to understand the molecular basis of radiation impact on T-lymphocyte subpopulations.

Spermatogenesis-associated protein 2 (SPATA2) is primarily named for its important role in spermatogenesis. Its function in tumorigenesis remains elusive. Here, we used various bioinformatic tools to systematically analyze the expression patterns of SPATA2 in cancers, the correlation of SPATA2 expression with clinical parameters, genetic variation, methylation, phosphorylation, immune infiltration and immune therapy. SPATA2 is significantly upregulated in multiple cancers and its expression was associated with tumor stage, grade and serve as a potential prognostic marker in LIHC. Notably, SPATA2 was also linked to immune suppression, exhibiting positive correlations with immune checkpoint genes and immune suppressive cells such as regulatory T cells and MDSCs. Furthermore, SPATA2 interacted and co-expressed with proteins involved in DNA repair mechanisms, indicating its potential role in maintaining genomic stability. Finally, we conducted biological experiments to investigate the role of SPATA2 in LIHC. SPATA2 knockdown enhances the migration and proliferation capabilities of Hep-G2 and HuH7 cell lines. These findings underscore the significance of SPATA2 in cancer biology, suggests its role in both the tumor microenvironment and the tumor cell level and its potential as a prognostic marker and therapeutic target in oncology, particularly in LIHC.

Combining immune checkpoint blockade (ICB) with chemotherapy shows promise for treating triple-negative breast cancer (TNBC), though the mechanisms remain incompletely understood. Here, we integrate published and new single-cell RNA sequencing (scRNA-seq) data to investigate the tumor immune microenvironment (TIME) in TNBC patients treated with paclitaxel (PTX), nab-paclitaxel (Nab-PTX), and their combinations with the anti-PD-L1 antibody atezolizumab (ATZ). Compared to ATZ plus PTX, ATZ plus Nab-PTX rewires TCF7+ stem-like effector memory CD8+ T cells (Tsem) and CD4+ T follicular helper (Tfh) cells. Nab-paclitaxel, unlike PTX, also reshapes the myeloid compartment, expanding mast cells and pro-inflammatory macrophages. Our analyses in human TNBC and murine models underscore the crucial role of mast cells in orchestrating anti-tumor immune responses, likely by promoting the recruitment and activation of T and B cells. In vivo experiments demonstrate that activating mast cells alongside PD-L1 blockade attenuates TNBC progression, suggesting mast cells as a promising adjunct for enhancing ICB therapy efficacy.

T cells play diverse roles in cancer immunology, acting as tumor suppressors, cytotoxic effectors, enhancers of cytotoxic T lymphocyte responses and immune suppressors; providing memory and surveillance; modulating the tumor microenvironment (TME); or activating innate immune cells. However, cancer cells can disrupt T cell function, leading to T cell exhaustion and a weakened immune response against the tumor. The expression of exhausted T cell (Tex) markers plays a pivotal role in shaping the immune landscape of multiple cancers. Our aim was to systematically investigate the role of known T cell exhaustion (Tex) markers across multiple cancers while exploring their molecular interactions, mutation profiles, and potential implications for immunotherapy. The mRNA expression profile of six Tex markers, LAG-3, PDCD1, TIGIT, HAVCR2, CXCL13, and LAYN was investigated in pan-cancer. Utilizing data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), The Cancer Proteome Atlas (TCPA), and other repositories, we characterized the differential expression of the Tex markers, their association with the patients' survival outcome, and their mutation profile in multiple cancers. Additionally, we analyzed the effects on cancer-related pathways and immune infiltration within the TME, offering valuable insights into mechanisms of cancer immune evasion and progression. Finally, the correlation between their expression and sensitivity to multiple anti-cancer drugs was investigated extensively. Differential expression of all six markers was significantly associated with KIRC and poor prognosis in several cancers. They also played a potential activating role in apoptosis, EMT, and hormone ER pathways, as well as a potential inhibitory role in the DNA damage response and RTK oncogenic pathways. Infiltration of different immune cells was also found to be associated with the expression of the Tex-related genes in most cancer types. These findings underline that the reviving of exhausted T cells can be used to enhance the efficacy of immunotherapy in cancer patients.

Cancer remains a significant public health issue worldwide, standing as a primary contributor to global mortality, accounting for approximately 10 million fatalities in 2020 [...].

NUP62, a key component of the nuclear pore complex, is closely associated with cellular functions and cancer progression. However, its expression patterns, prognostic value, and relationship with tumour immunity and drug sensitivity across multiple cancers have not been systematically studied. This study used multi-omics analyses combined with experimental validation in gastric cancer to investigate the expression, functional characteristics, and clinical relevance of NUP62 in cancer.

Data from TCGA, GTEx, and CPTAC databases were used to analyse the expression, mutation characteristics, and clinical associations of NUP62. Tools such as SangerBox, TIMER 2.0, and GSEA were employed to evaluate the relationship between NUP62 and the tumour immune microenvironment, as well as its involvement in signalling pathways. Immunohistochemistry and RT-PCR were used to validate the expression of NUP62 in gastric cancer tissues. PRISM and CTRP databases were utilised to assess the correlation between NUP62 expression and drug sensitivity.

NUP62 was significantly upregulated in multiple cancers and was associated with poor prognosis in cancers such as clear cell renal carcinoma (KIRC), lower-grade glioma (LGG), and adrenocortical carcinoma (ACC), while playing a protective role in others, such as bladder cancer (BLCA) and stomach cancer (STAD). Functional analyses showed that NUP62 is involved in cell cycle regulation, DNA damage repair, and tumour immunity. High NUP62 expression was significantly correlated with increased infiltration of immune cells, such as macrophages and T cells, and a higher response rate to immunotherapy. Drug sensitivity analysis identified NUP62 as a marker of sensitivity to various chemotherapeutic agents. Validation experiments demonstrated that NUP62 mRNA and protein levels were significantly higher in gastric cancer tissues than in adjacent normal tissues.

NUP62 plays a critical role in multiple cancers and shows potential as a biomarker for cancer diagnosis, prognosis, and therapeutic response prediction. Its role in tumour immunity and signalling pathways highlights its potential as a target for immunotherapy and precision medicine.

Esophageal squamous cell carcinoma (ESCC) is a predominant and highly lethal form of esophageal cancer, with a five-year survival rate below 20%. Despite advancements, most patients are diagnosed at advanced stages, limiting effective treatment options. Multi-omics integration, encompassing somatic genomic alterations, inherited genetic mutations, transcriptomics, proteomics, metabolomics, and single-cell sequencing, has enabled the identification of distinct molecular subtypes of ESCC.

This article systematically reviewed the current status of molecular subtyping of ESCC based on big data, summarized unique subtypes with differing treatment responses and prognostic outcomes.

Key findings included subtype-specific genetic mutations, signaling pathway alterations, and metabolomic profiles, which offer novel biomarkers and therapeutic targets. Furthermore, this review discusses the link between molecular subtypes and immunotherapy efficacy, chemotherapy response, and drug development.

These insights highlight the potential of omics-based molecular typing to transform ESCC management and facilitate personalized treatment strategies.

The induction of apoptosis in tumor cells is a common target for the development of anti-tumor therapies; however, these therapies still leave patients at increased risk of disease recurrence. For example, apoptotic tumor cells can promote tumor growth and immune evasion via the secretion of metabolites, apoptotic extracellular vesicles, and induction of pro-tumorigenic macrophages. This paradox of apoptosis induction and the pro-tumorigenic effects of tumor cell apoptosis has begged the question of whether apoptosis is a suitable cancer therapy, and led to further explorations into other immunogenic cell death-based approaches. However, these strategies still face multiple challenges, the most critical of which is the tumor microenvironment. Contrary to the promotion of immune tolerance mediated by apoptotic tumor cells, apoptotic bodies with enriched tumor-related antigens have demonstrated great immunogenic potential, as evidenced by their ability to initiate systemic T-cell immune responses. These characteristics indicate that apoptotic body-based therapies could be ideal "in situ" extra-tumoral tumor vaccine candidates for the treatment of cancers, and further address the current issues with apoptosis-based or immunotherapy treatments. Although not yet tested clinically, apoptotic body-based vaccines have the potential to better treatment strategies and patient outcomes in the future.

Gamabufotalin (CS-6), a main active compound derived from Chinese medicine Chansu, exhibits a robust inhibitory effect on programmed death-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) cells. Despite its potential for tumor therapy, the medical application of CS-6 is constrained by its hydrophobic nature, lack of targeting capability, and weak immunogenic cell death (ICD) effect. To address these limitations and improve the therapeutic efficiency of this drug against metastatic TNBC, we designed a new kind of CS-6@CPB-S.lux that integrates carboxy-Prussian blue nanoparticles (CPB NPs), CS-6, and attenuated Salmonella typhimurium (S.lux) for TNBC therapy. In vitro and in vivo results have confirmed that CS-6@CPB NPs were efficiently delivered to neoplastic tissue by the tumor hypoxic chemotaxis property of S.lux, wherein the nanomedicine induced significant tumor cell necroptosis and apoptosis via photothermal therapy (PTT) of CPB NPs and chemotherapy of CS-6, which elicited ICD and inhibited PD-L1 expression, resulting in dendritic cells (DCs) maturation and effector T cells activation to comprehensively eliminate tumors. Additionally, the CS-6@CPB-S.lux + Laser treatment significantly transformed the immunosuppressive tumor microenvironment (TME), enhancing antitumor immunity through promoting the polarization of tumor-associated macrophages into antitumorigenic M1 and reducing Tregs recruitment. Consequently, this comprehensive therapy not only inhibited primary and abscopal tumor progression but also prevented TNBC metastasis, which significantly prolonged survival time in animal models. In summary, these findings indicated an alternative approach for metastatic TNBC therapy.

The impacts of radiochemotherapy on peripheral blood cell and lymphocyte cell counts, immunoglobulin (Ig) and complement levels remain unclear. This study aims to investigate the above parameters regulated by radiotherapy (RT), induction chemotherapy (ICT) and concurrent chemotherapy (CCT) in head and neck cancer (HNC) patients.

Patients with non-metastatic HNC treated by conventional intensity-modulated radiation therapy (IMRT) were enrolled in this study. Data of peripheral blood cells, lymphocyte subpopulations, complements and immunoglobulins were collected before, during and after IMRT. And conducted regular follow-up on patients. SPSS (IBM, version 26.0), R (MathSoft, 4.0.3) and Graphpad Prism were used to perform statistical analysis and plot figures.

A total of 126 HNC patients undergoing RT were enrolled in this study. Among them, 44 patients received ICT, 56 patients received CCT, and 123 patients had complete survival information. Number of white blood cells (WBCs), platelets, basophils, total lymphocytes, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells declined significantly during RT. Accordingly, the ratio of help T cells to suppressor T cells (Th/Ts) and the percentages of B cells, CD4+ T cells also declined. There were increased levels of neutrophils and complement 4 (C4) and percentage of NK cells during RT. ICT caused significant reductions of platelets, B cells and immunoglobulin A (IgA). CCT reduced WBCs, red blood cells (RBCs), platelets, hemoglobin (HGB), granulocytes, total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells and immunoglobulin G (IgG). Generalized linear model (GLM) analysis further confirmed that RT was a risk factor for lower total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells, Th/Ts ratios, and lower percentages of B cells, CD4+ T cells. ICT contributed to decreased Th/Ts ratios, and immunoglobulin M (IgM) and IgA levels. As for CCT, it was an unfavorable factor for reduced total lymphocytes, B cells, CD4+ and CD8+ T cells, NK cells and IgG. Conversely, complement 3 (C3) or 4 levels were higher in patients treated with RT, ICT or CCT. Importantly, we found that HNC patients with higher lymphocytes or lymphocyte percentages like CD3+, CD4+ and CD8+ T cells before or after RT had a better prognosis. While higher NK cells and NK cell percentage before RT were associated with worse prognosis. In addition, higher levels of C3 and C4 before and after RT were associated with a favorable prognosis. However, higher levels of IgA, immunoglobulin E (IgE), IgG, and IgM before RT were associated with poorer prognosis.

To sum up, chemoradiotherapy resulted in significant alterations in peripheral immune biomarkers which in return influenced HNC patients' survival.

Clear cell renal cell carcinoma (ccRCC) is a lethal urological cancer that accounts for a considerable portion of all malignant tumors in adults. Alterations in mitochondrial function and metabolism may influence the onset and progression of ccRCC. This study aims to develop a novel clinical prognostic signature for ccRCC based on mitochondria-associated genes, as well as to identify new potential therapeutic agents for this condition.

A total of 539 ccRCC tumors and 72 normal kidney specimens were analyzed from The Cancer Genome Atlas (TCGA). We created a prognostic signature based on univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) Cox regression. A differential expression analysis, functional enrichment, and assessment of tumor immune cell infiltration were performed. Connectivity Map (CMap) and L1000CDS2 dataset were utilized for potential therapeutic drug identification. Vorinostat was examined for its effects on ccRCC cell proliferation, cell death, migration, and invasion using Cell Counting Kit-8 (CCK-8), lactate dehydrogenase (LDH) release, wound healing, and transwell assays.

The prognostic signature, comprising 16 mitochondria-related genes, demonstrated marked changes in overall survival between high- and low-risk groups. Functional analysis implicated immune-related pathways, indicating potential for immunotherapy strategies. Vorinostat, identified through drug screening, exhibited inhibitory implications on ccRCC cell proliferation, migration, and invasion and induced cell death.

The constructed prognostic signature provides a valuable tool for patient prognosis prediction. Vorinostat emerges as a promising therapeutic candidate for high-risk ccRCC patients, contributing to a deeper understanding of ccRCC biology and personalized therapeutic interventions.

Neuroblastoma (NB) is an immunologically "cold" tumor with poor or no inflamed substrates as most of solid pediatric tumors (SPT). Consistent data indicate that NB tumor microenvironment (TME) is dominated by myeloid cells, with little (but variable) T cell infiltration. The obstacles to lymphocyte infiltration and to their anti-tumor activity are due to different tumor immune evasion strategies, including loss of HLA Class I molecules, high expression of immune checkpoint molecular ligands leading to exhaustion of T effector (and NK) cells, induction of T regulatory, myeloid and stromal cells and secretion of immunosuppressive mediators. In odds with adult solid tumors, NB displays weak immunogenicity caused by intrinsic low mutational burden and scant expression of neoepitopes in the context of MHC-class I antigens which, in turn, are particularly poorly expressed on NB cells, thus inducing low anti-tumor T cell responses. In addition, NB is generated from embryonal cells and is the result of transcriptional abnormalities and not of the accumulation of genetic mutations over time, thus further explaining the low immunogenicity. The poor expression of immunogenic molecules on tumor cells is associated with the high production of immunosuppressive factors which further downregulate lymphocyte infiltration and activity, thus explaining the limited efficacy of new drugs in NB, as immune checkpoint inhibitors. This review is focused on examining the role of T effector and regulatory cells infiltrating TME of NB, taking into account their repertoire, phenotype, function, plasticity and, importantly, predictive value for defining novel targets for therapy.

Pancreatic cancer has one of the worst prognoses of any malignant tumor. The value of MIDN, midnolin-related genes and midnolin-related immune infiltrating cells (MICs) in the prognosis of pancreatic cancer remains unknown.

Single-cell analysis were used to identify midnolin-related genes. Immune cell infiltration was obtained using CIBERSORT. The prognostic midnolin-related genes were identified through the utilization of Cox regression and the least absolute selection operator (LASSO) approach. The combined prognostic model was created using multifactorial Cox regression analysis. Survival analyses, immune microenvironment assessments, drug sensitivity checks were performed to evaluate the combined model performance. Finally, cellular experiments were carried out to confirm MIDN significance in pancreatic cancer.

The combined model was constructed based on MIDN expression, prognostic model of 10 midnolin-related genes and M1 cell infiltration. Most immune checkpoint-related genes were expressed at greater levels in the low-risk group, suggesting a greater chance of immunotherapy's benefits. The most significant model gene, MIDN, was shown to have a function by cellular tests. In pancreatic cancer, MIDN knockdown drastically decreased pancreatic cancer cell lines' activity, proliferation, and invasive potential.

The combined model helped assess the prognosis of pancreatic cancer and offered fresh perspectives on immunotherapy in particular.

Although most cancer deaths are caused by metastasis, there are no effective therapeutic approaches. This study describes the efficacy of a short synthetic mRNA (s-mRNA) designed by the sequence of non-vesicular extracellular IL1β-mRNA found in the pre-metastatic lung of tumor-bearing mice. The administration of s-mRNA inhibits murine lung metastasis by inducing the innate and adaptive immune systems. s-mRNA binds to ZC3H12D, an RNA-binding protein on natural killer cells and cytotoxic T lymphocytes. The ZC3H12D-s-mRNA complex translocated to the nucleus without being involved in translation. This process induces cytolytic activity and cell death in cancer cells without inducing a cytokine storm, and immune cells retain their antitumor activity. Although the antitumor activity of cytotoxic lymphocytes declines as the disease progresses in cancer patients, s-mRNA induces sustained high killing capacities of natural killer cells and cytotoxic T lymphocytes from colon cancer patients. Therefore, s-mRNA could be a breakthrough solution to prevent metastasis.

Lung adenocarcinoma (LUAD) is a prevalent form of lung cancer globally, known for its high invasiveness, metastatic potential, and notable heterogeneity, particularly in its response to immunotherapy. Gremlin 1 (GREM1) is implicated in tumor progression and poor prognosis in multiple cancers. However, GREM1's specific role in LUAD remains unclear. This study systematically examines GREM1 expression in LUAD and its association with tumor progression, immune microenvironment, and prognosis.

Gene expression data from the TCGA and GSE31210 databases were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), GO and KEGG enrichment analyses. The prognostic value of GREM1 was evaluated through survival analysis, Cox regression, and Kaplan-Meier curves. Additionally, immune microenvironment analysis was conducted to explore the relationship between GREM1 and immune cell infiltration. In vitro experiments, including Western blot and assays for cell proliferation, migration, and invasion, were performed to confirm the specific role of GREM1 in LUAD cells.

GREM1 was significantly upregulated in tumor tissues and correlated with poor prognosis. Moreover, GREM1 was significantly associated with immune cell infiltration and immunotherapy response within the immune microenvironment. In vitro experiments confirmed that GREM1 overexpression significantly promoted LUAD cell proliferation, migration, and epithelial-mesenchymal transition (EMT), whereas GREM1 knockdown suppressed these functions.

A comprehensive analysis indicates that GREM1 is crucial in LUAD progression, with its overexpression predicting poor prognosis. GREM1 could be a potential therapeutic target for LUAD, providing insights for personalized therapy optimization.

N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotes, plays a critical role in the development and progression of various diseases, including cancer, through its regulation of RNA degradation, stabilization, splicing, and cap-independent translation. Emerging evidence underscores the significant role of m6A modifications in both pro-tumorigenic and anti-tumorigenic immune responses. In this review, we provide a comprehensive overview of m6A modifications and examine the relationship between m6A regulators and cancer immune responses. Additionally, we summarize recent advances in understanding how m6A modifications influence tumor immune responses by directly modulating immune cells (e.g., dendritic cells, tumor-associated macrophages, and T cells) and indirectly affecting cancer cells via mechanisms such as cytokine and chemokine regulation, modulation of cell surface molecules, and metabolic reprogramming. Furthermore, we explore the potential synergistic effects of targeting m6A regulators in combination with immune checkpoint inhibitor (ICI) therapies. Together, this review consolidates current knowledge on the role of m6A-mediated regulation in tumor immunity, offering insights into how a deeper understanding of these modifications may identify patients who are most likely to benefit from immunotherapies.

The median overall survival (OS) is approximately 10 months when chemotherapy alone is the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). The approval of the two PD-L1 inhibitors, atezolizumab and durvalumab, marked the beginning of the immunotherapy era for ES-SCLC. Serplulimab, as the first PD-1 inhibitor to achieve success in the first-line treatment of ES-SCLC, has not only demonstrated significant improvements in patient survival outcomes but also ushered in a new era for PD-1 inhibitors in the treatment of ES-SCLC. Recently, antiangiogenic agents with chemo-immunotherapy have achieved breakthroughs in first-line ES-SCLC treatment. Improving the clinical benefits of individualized treatment for patients with ES-SCLC remains challenging. Challenges include identifying biomarkers for targeted therapy, exploring new treatments, developing new medicines, and classifying SCLC molecular subtypes. This review provides an in-depth analysis of research on first-line ES-SCLC treatment. Additionally, it discusses advances in ES-SCLC treatment.

Postoperative pneumonia significantly affects recovery and prognosis in patients with esophageal squamous cell carcinoma. The CALLY index, derived from preoperative hematological parameters, may serve as a predictive marker for such complications.

To assess the association between preoperative inflammatory status via the CALLY index and the occurrence of postoperative pneumonia in patients with resectable ESCC.

A retrospective cohort study was conducted from January 2020 to December 2022 at The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University. A total of 215 patients who met inclusion criteria were analyzed. Clinical data, including CALLY indices calculated preoperatively, were collected. Propensity score matching was applied to minimize confounding biases. The predictive value of the CALLY index was assessed using receiver operating characteristic analysis, and logistic regression was used to identify factors associated with postoperative pneumonia.

ROC curve analysis demonstrated the CALLY index had an area under the curve of 0.764 for predicting postoperative pneumonia, with a cutoff value of 1.97 achieving 67.69% sensitivity and 84.67% specificity. In multivariate analysis, a lower CALLY index was significantly associated with increased pneumonia risk, independent of other factors (adjusted OR = 0.66, p < 0.001). High CALLY index scores correlated with a decreased likelihood of postoperative pneumonia, reinforcing its utility as a non-invasive prognostic marker.

The CALLY index is a robust, independent predictor of postoperative pneumonia in patients with resectable ESCC. Preoperative assessment of this index could enhance risk stratification and guide proactive management strategies to improve postoperative outcomes.

Tumor cells are known to enhance glycolysis, even under normoxic conditions, via the Warburg effect, producing excess lactic acid in the tumor microenvironment. Lactic acid enhances the IL-23/IL-17 pathway and induces chronic inflammation. The acidic microenvironment formed by lactic acid suppresses immune cell proliferation and activation. In the present study, we clarified that lactic acid had two novel activities for immune cells. First, lactic acid specifically enhanced acetylation at lysine 27 of histone H3 (H3K27ac) in splenic B cells and monocytes/macrophages, and this epigenetically up-regulates the expression of genes. Acetylation and methylation of other residues of histone H3 were rarely induced. Second, lactic acid induced a particularly-marked enhancement of Il10 gene expression in B cells, leading to an increase in IL-10-producing regulatory B (Breg) cells. Furthermore, two pathways should be involved in both the enhancement of H3K27ac and the induction of Breg cells by lactic acid: a direct pathway that enhances the CD40 signal in B cells, and an indirect pathway that affects B cells by activating the exchange protein directly activated by cAMP (EPAC) 1/2 in non-B cells. In tumor-bearing mice, the levels of H3K27ac of tumor-infiltrating B cells were significantly higher than splenic B cells and were suppressed by intraperitoneal injection of the EPAC1/2 inhibitor. In conclusion, tumor-derived lactic acid increases H3K27ac and IL-10-producing Breg cells, causing the suppression of anti-tumor immunity.

In the realm of oncology, the tumor microenvironment (TME)-comprising extracellular matrix components, immune cells, fibroblasts, and endothelial cells-plays a pivotal role in tumorigenesis, progression, and response to therapeutic interventions. Initially, the TME exhibits tumor-suppressive properties that can inhibit malignant transformation. However, as the tumor progresses, various factors induce immune tolerance, resulting in TME behaving in a state that promotes tumor growth and metastasis in later stages. This state of immunosuppression is crucial as it enables TME to change from a role of killing tumor cells to a role of promoting tumor progression. Gastric cancer is a common malignant tumor of the gastrointestinal tract with an alarmingly high mortality rate. While chemotherapy has historically been the cornerstone of treatment, its efficacy in prolonging survival remains limited. The emergence of immunotherapy has opened new therapeutic pathways, yet the challenge of immune tolerance driven by the gastric cancer microenvironment complicates these efforts. This review aims to elucidate the intricate role of the TME in mediating immune tolerance in gastric cancer and to spotlight innovative strategies and clinical trials designed to enhance the efficacy of immunotherapeutic approaches. By providing a comprehensive theoretical framework, this review seeks to advance the understanding and application of immunotherapy in the treatment of gastric cancer, ultimately contributing to improved patient outcomes.

Photothermal therapy (PTT), a popular local treatment that uses heat to ablate tumors, has limited efficacy in addressing metastatic and deeply located tumors when used alone. Integrating PTT with immunotherapy not only yields a synergistic effect but also promotes cancer regression and confers the benefit of immune memory, which can surmount the challenges faced by PTT when used in isolation. Metal-based nanomaterials, renowned for their superior photothermal conversion efficiency and distinctive photochemical properties, have been extensively researched and applied in the field of PTT. This review summarizes the latest developments in combination therapies, with a specific focus on the combination of PTT and immune checkpoint therapy (ICT) for cancer treatment, including a comprehensive overview of the recent advancements in noble metal-based and 2D transition metal chalcogenides (TMDCs)-based photothermal agents, and their anticancer effect when combining PTT with immune checkpoint blockades (anti-CTLA-4 and anti-PD-L1) therapy. The goal of this review is to present an overview of the application, current challenges and future prospects of metal-based photothermal agents in PTT combined with ICT for cancer treatment.

Histone deacetylase 3 (HDAC3) has emerged as a critical epigenetic regulator in tumor progression and immune modulation, positioning it as a promising target for enhancing cancer immunotherapy. This work comprehensively explores HDAC3's multifaceted roles, focusing on its regulation of key immune-modulatory pathways such as cGAS-STING, ferroptosis, and the Nrf2/HO-1 axis. These pathways are central to tumor immune evasion, antigen presentation, and immune cell activation. Additionally, the distinct effects of HDAC3 on various immune cell types-including its role in enhancing T cell activation, restoring NK cell cytotoxicity, promoting dendritic cell maturation, and modulating macrophage polarization-are thoroughly examined. These findings underscore HDAC3's capacity to reshape the tumor immune microenvironment, converting immunologically "cold tumors" into "hot tumors" and thereby increasing their responsiveness to immunotherapy. The therapeutic potential of HDAC3 inhibitors is highlighted, both as standalone agents and in combination with immune checkpoint inhibitors, to overcome resistance and improve treatment efficacy. Innovative strategies, such as the development of selective HDAC3 inhibitors, advanced nano-delivery systems, and integration with photodynamic or photothermal therapies, are proposed to enhance treatment precision and minimize toxicity. By addressing challenges such as toxicity, patient heterogeneity, and resistance mechanisms, this study provides a forward-looking perspective on the clinical application of HDAC3 inhibitors. It highlights its significant potential in personalized cancer immunotherapy, paving the way for more effective treatments and improved outcomes for cancer patients.

Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new immunotherapy strategies is essential.

We obtained RNA sequencing data and clinical information of colorectal cancer patients from the TCGA and GEO databases. The impact of the BRAF V600E mutation on tumor microenvironment characteristics, gene expression, and signaling pathways was evaluated using bioinformatics approaches. Weighted gene co-expression network analysis (WGCNA) were used to identify core genes associated with T cell dysfunction. Consensus clustering was applied for subtype construction. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithms were employed to filter potential immunotherapy targets.

We found that BRAF V600E mutation has a complex impact on the immune profile of colorectal cancer. It increases immune cell infiltration and activates immune-related signaling pathways, yet it also severely restricts T cell function. We subsequently identified 39 core genes associated with T cell dysfunction and constructed subtypes of BRAF V600E colorectal cancer based on their expression profiles. Significant heterogeneity was observed between these subtypes in immune signaling pathway activity, immune infiltration patterns, immune phenotype scores, and mechanisms of resistance to immunotherapy. Ultimately, using machine learning algorithms and bioinformatics validation, we identified IDO1 as a potential immunotherapy targets for BRAF V600E-mutant colorectal cancer.

This study constructed novel T cell dysfunction molecular subtypes for BRAF V600E-mutant colorectal cancer and identified IDO1 as a potential immunotherapy target, providing a new strategy for immunotherapy.

Liver cancer ranks among the deadliest cancers worldwide. Entosis, a recently uncovered method of cell death, has not yet been fully explored for its relevance to HCC. A bioinformatics analysis was performed to determine the expression and mutational landscapes of Entosis-related genes (ERGs). A subset of differentially expressed Entosis-related genes (DEERGs) was generated. A risk model for entosis was subsequently constructed employing LASSO and Cox regression methodologies. The correlations among ERGs, genes associated with risk, the developed risk model, and the immune context of the tumour were explored. Furthermore, the study investigated the varying drug sensitivities between high-risk and slight-risk patient groups. The expression patterns of four pivotal risk genes were delineated via qRT‒PCR and WB. A prognostic model comprising four DEERGs (KIF18A, SPP1, LCAT and TRIB3) was developed. The ability of this model to predict the survival outcomes of patients with HCC was confirmed through receiver operating characteristic curve analysis. Patients were grouped according to their risk assessments, revealing that the low-risk population demonstrated a more favourable survival outcome than did the high-risk population. The high-risk population presented reduced tumour stroma, immune and ESTIMATE scores, along with an increased proportion of cancer stem cells and tumour mutation burden. Additionally, a connection between the risk model and the responsiveness of various chemotherapy drugs as well as the efficacy of immunotherapies in patients was noted. These findings provide significant guidance for the development of targeted clinical treatment strategies. qRT‒PCR and WB analysis revealed that the gene expression of KIF18A and SPP1 were elevated in HCCLM3 cells compared with that in THLE2 cells; whereas, the expression level of LCAT and TIRB3 was decreased. The four genes KIF18A, SPP1, LCAT and TRIB3 could effectively predict the survival prognosis of patients with liver cancer. KIF18A and SPP1 were elevated in HCC tissues compared with that in THLE2 cells.

For most colorectal cancer (CRC) patients, expanding the benefits of immunotherapy, particularly through blocking programmed cell death-1 (PD-1) and its ligand (PD-L1), is crucial, especially in cases with limited response to neoadjuvant therapy. This study investigates the role of Myoferlin (MYOF) as a novel target in CRC immunotherapy.

Human CRC cell lines (RKO, HCT116), normal intestinal epithelial cells (HIEC-6), and the murine CRC cell line MC38 were used to study the effects of apatinib and MYOF in CRC cells. RNA sequencing, the CPTAC and TCGA databases, and other molecular and cellular methods were applied to disclose the mechanisms involved. A series of mouse models were established to assess the effects of apatinib and MYOF knockdown on tumor progression, immune cell infiltration, and immune checkpoint protein response.

We found that MYOF is overexpressed in CRC and linked to immune cell infiltration and checkpoint expression. Suppression of MYOF expression significantly inhibited CRC cell proliferation and migration, as well as reduced PD-L1 protein levels. Integrative analysis showed that apatinib modulates MYOF expression via VEGFR2, resulting in decreased PD-L1 expression, increased CD8+ T cell infiltration, and reduced pro-tumor M2 macrophages. Animal experiments further revealed that apatinib treatment or MYOF knockdown enhanced the efficacy of immune checkpoint blockade (ICB) in CRC.

These findings highlight novel antitumor mechanisms of MYOF and suggest that combining apatinib with ICB therapy may improve CRC treatment outcomes, offering a promising strategy to enhance immune responses.

As natural agonists of the stimulator of interferon genes (STING) protein, cyclic dinucleotides (CDNs) can activate the STING pathway, leading to the expression of type I interferons and various cytokines. Efficient activation of the STING pathway in antigen-presenting cells (APCs) and tumor cells is crucial for antitumor immune response. Tumor-derived exosomes can be effectively internalized by APCs and tumor cells and have excellent potential to deliver CDNs to the cytoplasm of APCs and tumor cells. Here, we leverage tumor exosomes as a delivery platform, designing an EXOTLR1/2-STING loaded with CDNs. To achieve efficient loading of CDNs onto exosomes, we chemically conjugated CDNs with Pam3CSK4, a compound featuring multiple fatty acid chains, resulting in Pam3CSK4-CDGSF. Utilizing the high lipophilicity of Pam3CSK4, Pam3CSK4-CDGSF could be efficiently loaded onto the exosomes through simple incubation. Moreover, as an agonist for Toll-like receptor 1/2, Pam3CSK4 also exhibits robust immunological synergistic effects in conjunction with CDNs. EXOTLR1/2-STING effectively induced the activation of APCs and triggered tumor cell death, producing a favorable antitumor therapeutic effect. It also demonstrated significant synergistic effects with immune checkpoint therapies.