Journal for Immunotherapy of Cancer最新文献

{"title":"Oncolytic adenovirus-mediated delivery of anti-CLDN18.2 IgG3 for the treatment of solid tumors.","authors":"Lei Pei, Wanrong Zhang, Haoran Zhu, Xin Xu, Qingguo Guo, Yuan Meng, Wei Pang, Yifan Zhang, Wanyang Zeng, Mingrui Ma, Ying Liu, Guangzuo Luo","doi":"10.1136/jitc-2026-015661","DOIUrl":"10.1136/jitc-2026-015661","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XIAP inhibition augments personalized neoantigen vaccine-driven antitumor immunity in orthotopic hepatocellular carcinoma.","authors":"Xiaoyuan Zheng, Jun Fu, Geng Chen, Yao Huang, Junjing Huang, Zhenli Li, Wenting Zhong, Bingchen Wu, Ruijing Tang, Yanv Yue, Tingfeng Huang, Lingtian Meng, Pan Mou, Peizhe Chen, Luobin Guo, Xiuqing Dong, Xiaolong Liu, Yongyi Zeng, Zhixiong Cai","doi":"10.1136/jitc-2026-014831","DOIUrl":"10.1136/jitc-2026-014831","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-delivered CD3×CD19 T-cell engager by STAb-T19 cells mediates leukemia clearance with limited systemic exposure.","authors":"Laura Sanz-Ortega, Elena Barba-Sarasúa, Ivana Zagorac, Antonio Tapia-Galisteo, Lucía Rivas-Gómez, Noelia López, Belén Blanco, Carolina Pola, Luis Alvarez-Vallina","doi":"10.1136/jitc-2026-015573","DOIUrl":"10.1136/jitc-2026-015573","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic body radiation therapy enriches mediators of humoral immune activity in metastatic renal cell carcinoma.","authors":"Nicholas J Salgia, Adil Khan, Yu Fujiwara, Mark Long, Gavin C Twoey, Kyle Leatt, Jacky Chow, Scott I Abrams, Thomas Schwaab, Anurag K Singh, Jason B Muhitch","doi":"10.1136/jitc-2026-015849","DOIUrl":"10.1136/jitc-2026-015849","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopic rabphilin-3A expression in lung adenocarcinoma associated with paraneoplastic arginine vasopressin deficiency during anti-PD-L1 therapy: a case report.","authors":"Haruki Fujisawa, Yosuke Eguchi, Naoko Iwata, Masaaki Kobayashi, Tsuyoshi Hattori, Kaori Ushida, Taiga Takahashi, Naoya Asai, Naoki Ijiri, Atsushi Suzuki, Yoshihisa Sugimura","doi":"10.1136/jitc-2026-015624","DOIUrl":"10.1136/jitc-2026-015624","url":null,"abstract":"","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCASIA: an integrative atlas linking alternative splicing landscapes for cancer immunotherapy.","authors":"Yihao Zhang, Yunzhi Guo, Haitao Wang, Yi Xiong, Minjun Chen, Ying Cai, Xin Li, Jun Wu, Jiaqi Hao, Su-Han Jin, Wei Zhang, Luohuan Dai, Hongwei Liu, Jianfeng Li, Jiahui Zhang, Markus Hecht, Benjamin Frey, Udo S Gaipl, Xin Chen, Xuejun Li, Shixiang Wang, Hu Ma, Jian-Guo Zhou","doi":"10.1136/jitc-2026-015364","DOIUrl":"10.1136/jitc-2026-015364","url":null,"abstract":"<p><strong>Background: </strong>Identifying robust predictive biomarkers for immune checkpoint blockade (ICB) remains a challenge. While alternative splicing (AS) shapes tumor immunity, the lack of large-scale, consensus-based datasets constrains the characterization of ICB-specific splicing landscapes.</p><p><strong>Methods: </strong>We developed TCASIA (the Cancer Alternative Splicing Immunotherapy Atlas), harmonizing >4000 samples across 29 cohorts. A rigorous \"2-out-of-4\" multi-algorithm consensus framework (rMATS, MAJIQ, SUPPA2, and SplAdder) with a fuzzy matching strategy was used to establish a high-confidence AS landscape.</p><p><strong>Results: </strong>TCASIA provides a robust toolkit linking splicing perturbations with clinical phenotypes (response, survival, and immune infiltration). Using this platform, we recapitulated the established <i>FAS</i> exon 6 skipping mechanism and identified <i>IL7R</i> exon 6 skipping as a functionally supported candidate associated with reduced CD8⁺ T-cell infiltration and poor survival in melanoma.</p><p><strong>Conclusions: </strong>TCASIA provides an analytical atlas for investigating splicing-mediated immune evasion and prioritizing isoform-specific candidates for further functional and clinical validation in the context of ICB treatment.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of adjuvant therapy on melanoma-specific survival in elderly patients with high-risk resected melanoma: a multicenter international retrospective study.","authors":"Andrea Boutros, Janet McKeown, Roger Olofsson Bagge, Lars Ny, Jan Mattsson, Francesco Spagnolo, Enrica Teresa Tanda, Ralf Gutzmer, Piyush Grover, Lydia Warburton, Muhammad Adnan Khattak, Douglas B Johnson, Kyle P Maas, Hannah Burnette, Ryan J Sullivan, Derek Effiom, Aleigha R Lawless, Paolo A Ascierto, Vito Vanella, Caroline Gaudy-Marqueste, Nausicaa Malissen, Tobias Peres, Anadil Javaid, Praveena Idaikkadar, Celeste Lebbé, Laetitia Da Meda, Hazel Burke, Ines Pires da Silva, Alexander C J van Akkooi, Matteo S Carlino, Serigne N Lo, Georgina V Long, Alexander M Menzies","doi":"10.1136/jitc-2026-016060","DOIUrl":"10.1136/jitc-2026-016060","url":null,"abstract":"<p><strong>Purpose: </strong>Adjuvant systemic therapy improves recurrence-free survival in resected high-risk melanoma, but elderly patients remain markedly under-represented in clinical trials; their competing risk of death from other causes needs to be considered. Consequently, the clinical benefit of adjuvant therapy in older populations remains uncertain. We conducted an international real-world study to evaluate survival outcomes of patients aged ≥75 years with resected stage III-IV melanoma managed with adjuvant systemic therapy or observation.</p><p><strong>Methods: </strong>In this multicenter retrospective cohort study, patients aged ≥75 years with completely resected stage III-IV cutaneous melanoma were identified across 14 international melanoma centers. Patients received either standard adjuvant systemic therapy (anti-programmed cell death protein 1 immunotherapy or BRAF/MEK-targeted therapy) or observation. The primary endpoint were melanoma-specific survival (MSS) and overall survival (OS). Secondary endpoints included recurrence-free survival (RFS). Survival outcomes were estimated using Kaplan-Meier methods and evaluated with multivariable Cox regression models adjusted for age, stage, sex, and mutation status.</p><p><strong>Results: </strong>A total of 580 patients were included (median age 79 years; range, 75-99), of whom 222 (38%) received adjuvant therapy and 358 (62%) underwent observation. Adjuvant therapy was associated with significantly improved MSS, with 5-year MSS of 74% compared with 60% in the observation group (adjusted HR 0.58; 95% CI 0.40 to 0.85; p=0.005), as well as OS (adjusted HR 0.66, 95% CI 0.51 to 0.87; p=0.002). Adjuvant therapy was also associated with improved RFS (HR 0.57, 95% CI 0.45 to 0.72; p<0.0001). Among patients managed with observation, disease recurrence occurred in 69%, yet only 47% of those patients received systemic therapy as first-line management of recurrence. Notably, among observation patients who remained recurrence-free or received systemic therapy after recurrence, MSS was comparable to that observed in adjuvant-treated patients (HR 0.83; 95% CI 0.55 to 1.25).</p><p><strong>Conclusion: </strong>In this large international real-world cohort of elderly patients with resected melanoma, adjuvant therapy was associated with clinically meaningful improvements in MSS, OS and RFS. Although immunotherapy retained efficacy when administered at recurrence, many elderly patients did not receive systemic therapy as first-line management of recurrence. Adjuvant therapy may therefore represent an important strategy to ensure timely access to effective treatment in carefully selected older patients.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP1-selective inhibitor DSB1559 demonstrates superior efficacy and antitumor immunity in triple-negative breast cancer.","authors":"Adam Nelson, Kelly F Zheng, Carlos Wagner S Wanderley, Daniel E Michaud, Phillip M Cowley, Gillian M Campbell, Bose Kochupurakkal, Yuqing Jiao, Carman Man-Chung Li, Filipa Lynce, Geoffrey I Shapiro, Barry E McGuinness, Alan Wise, Jennifer L Guerriero","doi":"10.1136/jitc-2025-014578","DOIUrl":"10.1136/jitc-2025-014578","url":null,"abstract":"<p><strong>Background: </strong>Poly (ADP-ribose) polymerase inhibitors (PARPis) have improved outcomes of BRCA-associated breast cancer; however, treatment-related toxicity remains a major clinical challenge. Currently approved PARPis broadly inhibit multiple members of the PARP protein family. However, preclinical studies suggest that inhibition of PARP1 alone is sufficient to drive antitumor efficacy. In contrast, inhibition of PARP2 has been implicated in hematological toxicities seen in patients receiving PARPi therapy. Therefore, selectively inhibiting PARP1 may reduce toxicity for patients. Here, we characterize and test the PARP1-selective inhibitor DSB1559 in preclinical models of Brca1-associated triple-negative breast cancer (TNBC).</p><p><strong>Methods: </strong>Pharmacokinetic/pharmacodynamic assays were performed to examine DSB1559 potency, selectivity, and in vivo behavior. Immunocompetent FVB/n mice bearing Brca1-deficient TNBC (CMV-Cre;Brca1^fl/fl;Trp53^fl/fl) tumors were treated with olaparib or DSB1559 and followed for survival. Flow cytometry and bulk RNA-sequencing were performed to measure the effects on the tumor microenvironment (TME).</p><p><strong>Results: </strong>DSB1559 had superior selectivity for PARP1 and increased overall survival compared with olaparib. Analysis of the TME revealed a significant increase in cytotoxic T-cells, activated dendritic cells, and genes associated with antitumor immunity in mice treated with DSB1559.</p><p><strong>Conclusions: </strong>Taken together, DSB1559 is a highly selective PARP1 inhibitor that demonstrates superior efficacy and antitumor immune response compared with olaparib. A structurally related, clinical lead compound (DSB2455) is now being tested in a phase Ia/Ib clinical trial (NCT06458712).</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD6 in solid tumors: safety, early efficacy, and mechanistic insights from a proof-of-concept trial of itolizumab.","authors":"Cynthia González Muñoz, Raiza Ruiz-Lorente, Olivia Blanco-Pita, Noralys Lara-Fernández, Eva Elena Salomón, Alexis Alvárez Lobaina, Jenysbel de la Caridad Hernandez Reyes, Patricia Lorenzo-Luaces Álvarez, Mayelín Troche-Concepción, Loipa Medel Perez, Yanela Santiesteban-González, Daymys Estevez-Iglesias, Arasay Montes-D'Santis, Aymé Fernández-Calienes Valdés, Tania Crombet Ramos, Mayra Ramos Suzarte, Mayrel Labrada Mon","doi":"10.1136/jitc-2026-016182","DOIUrl":"10.1136/jitc-2026-016182","url":null,"abstract":"<p><strong>Background: </strong>CD6 is a promising target in cancer immunotherapy, with preclinical evidence supporting its role in modulating immune responses. This warrants further investigation into current CD6-targeting treatments, which could lead to new anti-tumor therapies. However, the clinical effects of targeting CD6 in solid tumors remain unexplored.</p><p><strong>Methods: </strong>This proof-of-concept study is the first in-human evaluation of the safety and early effectiveness of anti-CD6 monoclonal antibody itolizumab in patients with advanced, highly heterogeneous solid tumors. Treatment had two phases: induction and maintenance. In induction, group A received 100 mg weekly for nine doses; group B received 200 mg biweekly for five doses. After completing induction, patients moved to maintenance 21 days later, receiving 100 mg every 21 days for up to six doses. The primary endpoint was safety; secondary objectives included disease control, survival, and exploratory molecular mechanisms and blood biomarkers.</p><p><strong>Results: </strong>Itolizumab demonstrated a favorable safety profile, with no safety-related treatment discontinuations, no related serious adverse events, and no unexpected toxicities. In this heavily treated, non-biomarker-selected population, disease control was achieved in 25% in group A and 20% in group B, and the 1-year survival rate was 26% in group A and 15% in group B. Mechanistically, ex vivo analysis demonstrated that itolizumab downregulates CD6, increasing soluble CD6 levels and promoting a cytotoxic phenotype on CD8 and NK cells. Additionally, patient-derived peripheral blood mononuclear cells demonstrated boosted in vitro killing capacity specifically against CD318+ cancer cells. The antibody also modulates PD-1 expression in peripheral lymphocytes, promoting NK cell activity while maintaining inhibitory signals on CD8+ T cells and decreasing T helper overactivation. These findings support the dual role of itolizumab, enhancing anti-tumor responses while preventing autoimmune-like effects by reducing off-target inflammation and avoiding immune-related adverse effects associated with immune checkpoint therapies.</p><p><strong>Conclusions: </strong>Overall, these findings support further development of itolizumab as a rational immunomodulatory strategy with a favorable safety profile for advanced solid tumors, particularly in CD318-expressing tumors and as part of rational combination regimens.</p><p><strong>Trial registration number: </strong>RPCEC00000444.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL7R mRNA therapy enhances antitumor T cell immunity and suppresses tumor growth in preclinical tumor models.","authors":"Adeel Ur Rehman, Muhammad Naveed Khan, Aleena Akhtar, Qianshan Qin, Xiaojing Zhang, Muhammad Arif Asghar, Dandan Ling, Pei Wang, Ying Luo, Zhihuai Wang, Lexin Wang, Hanyang Liu, Xiaosong Li","doi":"10.1136/jitc-2026-017160","DOIUrl":"10.1136/jitc-2026-017160","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-7 receptor (IL7R) signaling is critical for T-cell survival, homeostasis, and immune function, but the therapeutic potential of increasing IL7R expression through messenger RNA (mRNA) delivery remains poorly defined. We investigated whether IL7R mRNA therapy could enhance antitumor immunity and improve tumor control in preclinical cancer models.</p><p><strong>Methods: </strong>IL7R mRNA formulated in lipid nanoparticles (LNPs) was administered by combined intratumoral and intravenous injection in syngeneic B16 melanoma and Lewis lung carcinoma (LLC) models, with empty LNPs included as vehicle controls. Therapeutic efficacy, IL7R expression, immune responses, transcriptomic remodeling, T-cell receptor (TCR) repertoire changes, and treatment tolerability were evaluated using complementary molecular, immunological, and sequencing approaches.</p><p><strong>Results: </strong>IL7R mRNA treatment increased IL7R transcript and protein levels in tumor-bearing mice, whereas empty LNPs did not produce comparable increases. Treatment increased tumor-infiltrating CD8 T-cell frequencies, suppressed tumor growth and prolonged survival in both B16 and LLC models; empty LNP controls did not reproduce the therapeutic effect. Cytokine and transcriptomic analyses showed treatment-associated activation of inflammatory, T-cell, interferon, and antigen-receptor signaling programs. TCR sequencing further demonstrated increased repertoire diversity and reduced clonal dominance following IL7R mRNA treatment. No obvious body-weight loss or marked changes in serum alanine aminotransferase, aspartate aminotransferase, or creatinine were observed under the tested conditions.</p><p><strong>Conclusions: </strong>IL7R mRNA therapy increases IL7R expression and is associated with enhanced T-cell antitumor responses, tumor growth suppression, improved survival, and remodeling of the tumor immune environment. These findings support further mechanistic and preclinical evaluation of IL7R mRNA-based cancer immunotherapy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 10","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}