Journal of cancer immunology最新文献

{"title":"Predicting Durable Anti-tumor Immune Responses after Cancer Vaccines.","authors":"John B Liao, Mary L Disis","doi":"10.33696/cancerimmunol.8.119","DOIUrl":"10.33696/cancerimmunol.8.119","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"8 1","pages":"13-16"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cristae Architecture as a Metabolic Checkpoint in Effector T Cells - Implications for Cancer Immunity.","authors":"Prakash Jeysankar, Sonal Srikanth, Beibei Wu, Yousang Gwack","doi":"10.33696/cancerimmunol.8.120","DOIUrl":"10.33696/cancerimmunol.8.120","url":null,"abstract":"<p><p>Effector T cells rely on tightly coordinated metabolic and epigenetic programs to sustain immune function. Emerging evidence highlights a central role for mitochondria in integrating these programs through nutrient utilization and regulation of metabolite flux. The electron transport chain (ETC), localized to the inner mitochondrial membrane, directs cellular metabolism toward oxidative phosphorylation. The efficiency of ETC activity is governed by the highly folded architecture of the inner mitochondrial membrane into cristae. Although mitochondrial metabolism is well recognized as a key determinant of cellular metabolic states, the regulatory roles of cristae-organizing structural proteins, particularly in T cells, remain poorly defined. Our recent study identifies the inner mitochondrial membrane protein TMEM11 as a critical structural determinant of cristae organization and demonstrates how cristae integrity governs effector T cell function by controlling oxidative phosphorylation and metabolite flux. TMEM11 deficiency disrupts cristae architecture in T cells without affecting mitochondrial biogenesis or cell viability. Mechanistically, loss of TMEM11 impairs ETC function, leading to elevated mitochondrial reactive oxygen species (mtROS), which diverts acetyl-CoA away from histone acetylation toward fatty acid synthesis, thereby suppressing cytokine production. Collectively, these findings reveal a structural-metabolic-epigenetic axis that is essential for effector T cell immunity and suggest potential relevance for T cell-mediated cancer therapy.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"8 1","pages":"17-22"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Second-Line Systemic Therapies in Metastatic Renal Cell Carcinoma: Current Insights and Future Directions.","authors":"Isaac E Kim, Vivian Wong, Karie Runcie, Eric A Singer","doi":"10.33696/cancerimmunol.7.107","DOIUrl":"10.33696/cancerimmunol.7.107","url":null,"abstract":"<p><p>Over the past few decades, the incidence of renal cell carcinoma (RCC) has rapidly increased with a considerable portion of patients presenting with metastatic disease (mRCC) and subsequent poor prognosis. Survival drops even further for those whose diseases progress on first-line therapy including immune-checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this review, we highlight the main second-line systemic therapies including TKIs, mTOR inhibitors, ICIs, and HIF-2α inhibitors along with their mechanisms of action and supporting clinical trials. We also highlight ongoing trials investigating novel second-line therapies such as the LITESPARK-011 trial contrasting belzutifan/lenvatinib with cabozantinib and the ENTRATA study examining glutaminase inhibitors including telaglenastat. The recent wave of key clinical trials has substantially increased the therapeutic options available to patients whose diseases have progressed on ICIs or VEGFR-TKIs. However, survival outcomes and the quality of life of mRCC patients on second-line treatments are still relatively limited, indicating a need for continued innovation and drug development in the field and continued trial recruitment at high-volume cancer centers.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"7 2","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlighting the Role of DCLK1 in Tumor Invasion and Potential for Therapeutic Intervention.","authors":"Molly E Muehlebach, Sufi Mary Thomas","doi":"10.33696/cancerimmunol.7.116","DOIUrl":"10.33696/cancerimmunol.7.116","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 5% of global cancer deaths per year, with epidemiological studies suggesting an expected 30% increase in cases by 2030 due to rising incidence of viral infection (i.e. huma papilloma virus [HPV]). Treatment consists primarily of surgical tumor removal accompanied by post-operative chemoradiation therapy; however, disease recurrence is still an issue amongst 10-26% of patients. Doublecortin-like kinase 1 (DCLK1) is a microtubule-associated protein with dual kinase activity, and upregulation has been associated with poor prognosis in multiple solid tumors. Recent studies by Arnold <i>et al.</i> highlighted a definitive role of DCLK1 in HNSCC invadopodium formation and function, and has elucidated its potential for small molecule targeting. This commentary summarizes the molecular findings by Arnold <i>et al.</i> and evaluates them in regard to the current standings of DCLK1 targeting, emphasizing why inhibiting this molecule could be of clinical significance.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"7 4","pages":"174-180"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13030886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Reprogramming with DNMT Inhibitors: A Multi-Mechanistic Approach to Enhance Immunotherapy in Glioblastoma.","authors":"Thomas J Lai, Robert M Prins, Richard G Everson","doi":"10.33696/cancerimmunol.7.103","DOIUrl":"10.33696/cancerimmunol.7.103","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"7 1","pages":"39-44"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting FAK to Potentiate Immune Checkpoint Therapy in Solid Tumors.","authors":"Karly A Stanley, Sheri L Holmen","doi":"10.33696/cancerimmunol.7.109","DOIUrl":"10.33696/cancerimmunol.7.109","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibition revolutionized cancer care, yet many people will fail to respond due to innate or acquired resistance. Combination therapies with immune checkpoint inhibitors are being explored to enhance their efficacy and improve patient outcomes. Focal adhesion kinase (FAK), known for its roles in cell adhesion and migration, has emerged as a potential therapeutic target due to the identification of its additional functions in cancer progression, including its ability to establish a pro-tumorigenic, immunosuppressive microenvironment. FAK has the ability to create physical barriers for immune cell infiltration and drug delivery through its regulation of blood vessel formation and extracellular matrix in the tumor stroma. Additionally, FAK has been reported to function both within tumor and immune cells to inhibit immune cell recruitment, stimulation, and function. Taken together, FAK functions within cancer to dampen immune surveillance and promote immune escape. As a result, there is mounting interest in the use of FAK inhibitors in combination with immune checkpoint inhibition for the treatment of solid tumors, and this strategy is actively being explored in the pre-clinical and clinical setting. This article reviews the ways in which FAK alters the tumor microenvironment and the cells within it in order to assess the clinical potential of co-targeting FAK and immune checkpoints.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"7 3","pages":"99-108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherent Natural Killer Cells De Novo Express IL-2Rα and Sustain Long-Lasting, Potent Anti-Tumor Activity in Picomolar Concentrations of IL-2.","authors":"Nikola L Vujanovic, Lazar Vujanovic, Theresa L Whiteside","doi":"10.33696/cancerimmunol.7.110","DOIUrl":"10.33696/cancerimmunol.7.110","url":null,"abstract":"<p><p>Natural killer (NK) cells are innate lymphoid cells (ILCs) that play key roles in immunosurveillance and immunoregulation. They constitute a heterogeneous population comprising three principal subpopulations: NK1 (cytotoxic), NK2 (regulatory), and NK3 (adaptive). In response to interleukin-2 (IL-2) stimulation, NK3 cells differentiate into adherent NK (A-NK) cells, which exhibit potent anti-tumor activity. Human A-NK cells are generated by priming and adherence-based selection of peripheral blood NK3 cells in nanomolar (nM) IL-2 concentrations, followed by prolonged restimulation and culture in the same IL-2 conditions. However, these A-NK cells are terminally differentiated, unresponsive to IL-2, prone to apoptosis, and are ineffective in cancer therapy. Here, we report previously unrecognized physiological properties of A-NK cells and describe a novel strategy for their <i>in vitro</i> generation. Specifically, we demonstrate that A-NK cells primed with nM IL-2 concentrations <i>de novo</i> express the high-affinity IL-2 receptor (IL-2Rαβγ). Upon subsequent transfer to picomolar (pM) IL-2 concentrations, these cells undergo sustained vigorous proliferation and retain robust anti-tumor activity in long-term cultures. These findings underscore the functional plasticity of NK3 cells, demonstrating that nM IL-2 priming can reprogram them to function efficiently in pM IL-2 as highly effective anti-tumor effectors. This cytokine-mediated reprogramming of NK3 cells provides a physiologically relevant strategy for generating fully functional therapeutic NK cells with reduced IL-2 dependency. This approach offers a promising venue for advancing NK cell-based cancer immunotherapies.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"7 3","pages":"109-122"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13021156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers","authors":"Jake Drobner, Krishna Doppalapudi, B. Saraiya, V. Packiam, S. Ghodoussipour","doi":"10.33696/cancerimmunol.6.078","DOIUrl":"https://doi.org/10.33696/cancerimmunol.6.078","url":null,"abstract":"Introduction & Objective: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome’s role in modulating and predicting immunotherapy response to genitourinary malignancies.\u0000\u0000Methods: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed.\u0000\u0000Results: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers.\u0000\u0000Conclusions: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"11 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of a Training Simulator for Kidney Biopsy and Tumor Removal Procedures in Complex Positioning Scenarios: The Key Challenges","authors":"Trijit Reet Adhikary, Santu Paul, Anu Jayanthi Panicker, S. Dakua","doi":"10.33696/cancerimmunol.6.079","DOIUrl":"https://doi.org/10.33696/cancerimmunol.6.079","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"59 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Tumor-derived Small Extracellular Vesicles on T cell Survival in Patients with Cancer; A Commentary.","authors":"Theresa L Whiteside","doi":"10.33696/cancerimmunol.6.097","DOIUrl":"10.33696/cancerimmunol.6.097","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 4","pages":"162-168"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}