Journal for Immunotherapy of Cancer最新文献

{"title":"Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.","authors":"Eneko Garate-Soraluze, Iñigo Martinez-Zubiaurre, Maria E Rodriguez-Ruiz","doi":"10.1136/jitc-2024-009702","DOIUrl":"https://doi.org/10.1136/jitc-2024-009702","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are one of the main components of the tumor microenvironment (TME) of solid tumors. They have several functions, which all contribute to tumor growth and immune evasion. CAF presence is associated with poor clinical response to standard therapy and immunotherapy. However, its heterogeneity blunts their understanding and functionality. New analytical techniques are being applied to better understand their role in cancer. Meanwhile, CAF stratification and their immunomodulatory capabilities are the scope of many studies, also in the context of ionizing irradiation. In that regard, new immunotherapy strategies have set their sights on targeting CAF to modulate the TME into a more immune-stimulating environment. Among the different approaches, CAF depletion, reprogramming, and CAF-directed antibodies and cytokines can be distinguished, supported by substantial preclinical evidence and encouraging, but still preliminary clinical findings, mainly from early-phase (phase I) trials. Additionally, CAF-directed radionuclides have gained interest and are in clinical trials for therapeutic as well as diagnostic purposes. Here we summarize the studies and clinical developments of CAF-targeted therapies alone and in combination with radiotherapy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 5","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838068","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":"Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer.","authors":"Sasha E Stanton, Denise L Cecil, Howard H Bailey, Ying Liu, William R Gwin, Andrew L Colveler, John B Liao, Kari B Wisinski, Lisa Barroilhet, KyungMann Kim, Thomas C Havighurst, Katina DeShong, Kyleigh Twaroski, Jennifer S Childs, Eileen Dimond, Margaret Wojtowicz, Brandy M Heckman-Stoddard, Mary L Disis","doi":"10.1136/jitc-2025-014314","DOIUrl":"https://doi.org/10.1136/jitc-2025-014314","url":null,"abstract":"<p><strong>Background: </strong>Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. Current treatment consists of surgery, radiation, and often systemic therapy exposing patients to unnecessary health risks. Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer.</p><p><strong>Methods: </strong>We developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. We then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease. The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 µg) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level. Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity.</p><p><strong>Results: </strong>There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic; responders included 70% of participants at the 150 µg dose level, 67% at the 300 µg dose, and 40% at the 600 µg dose level. All participants at the 300 µg dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations. T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders.</p><p><strong>Conclusions: </strong>The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS.</p><p><strong>Trial registration number: </strong>NCT02780401.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 5","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838076","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":"Patient-derived organotypic tumor spheroids as a functional platform for predicting immunotherapeutic responses and guiding precision treatment for hepatocellular carcinoma.","authors":"Fei Song, Yi-Jun Lu, Hai-Xiang Sun, Jian-Wen Cheng, Wen-Zhen Li, Zhenhao Liu, Rui-Zhe Li, Peng-Xiang Wang, Wen-Jing Zheng, Yu-Chen Zhong, Yang Xu, Jie Xu, Yu Wang, Su-Yan Bai, Lu Xie, Kwan Man, Jia Fan, Jian Zhou, Zhong Chen, Xin-Rong Yang","doi":"10.1136/jitc-2025-014555","DOIUrl":"https://doi.org/10.1136/jitc-2025-014555","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While immune checkpoint blockade has revolutionized the treatment of many cancers, responses in HCC remain limited. Robust functional platforms capable of predicting individual responses to immunotherapy are urgently needed. In this study, we developed a patient-derived organotypic tumor spheroid (PDOTS) model that preserves the heterogeneity and immune microenvironment of HCC, enabling rapid and reliable assessment of targeted and immunotherapeutic responses.</p><p><strong>Methods: </strong>Tumor tissues from 30 HCC patients were processed using a \"Five-Point Clock\" sampling method and cultured within a three-dimensional microfluidic chip supplemented with IL-2 and CD3/28 activator to maintain tumor-infiltrating lymphocyte activity. The genomic, immune, and histopathological fidelity of PDOTS relative to parental tumors was evaluated. Drug responses were assessed ex vivo and validated in matched patient-derived xenograft (PDX) models. Transcriptomic profiling was subsequently performed to identify gene signatures associated with treatment sensitivity and to construct a transcriptomic predictive model.</p><p><strong>Results: </strong>The PDOTS retained ≥60% viability over 7 days and faithfully maintained the genomic, immune, and histopathological profiles of parental tumors. Functionally, PDOTS exhibited immune-dependent responses to PD-1 blockade and predicted treatment responses with 80% concordance in matched PDX models. Transcriptomic profiling revealed distinct metabolic and immune signatures in sensitive and resistant tumors, which were used to derive the \"Organoid Killing Index (OKI)\". The OKI gene-derived index, a composite index integrating the enrichment scores of gene signatures associated with the OKI, strongly correlated (<i>R</i>=0.829, p<0.001) and predicted clinical outcomes in an external patient cohort treated with atezolizumab plus bevacizumab.</p><p><strong>Conclusions: </strong>These findings establish PDOTS as an immune-competent ex vivo platform for functional precision oncology and support the integration of functional testing with transcriptomic prediction to guide individualized immunotherapy in HCC.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 5","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838078","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":"Phase 2 study of palbociclib plus retifanlimab in patients with advanced dedifferentiated liposarcoma.","authors":"Evan Rosenbaum, Kenneth Seier, Rodrigo Gularte-Mérida, Evan Seffar, Mark A Dickson, Viswatej Avutu, Lauren B Banks, Jason E Chan, Ping Chi, Mrinal M Gounder, Ciara M Kelly, Mary L Keohan, Robert G Maki, Sujana Movva, Damon Reed, Rhoena Desir, Matthew Biniakewitz, Jae-Mun Cho, Michele Duchemin, Joseph P Erinjeri, Robert A Lefkowitz, Andrew Koff, Samuel Singer, William Tap, Li-Xuan Qin, Sandra D'Angelo","doi":"10.1136/jitc-2025-014346","DOIUrl":"https://doi.org/10.1136/jitc-2025-014346","url":null,"abstract":"<p><strong>Background: </strong>The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib delays disease progression in dedifferentiated liposarcoma (DDLPS) by inducing tumor cell quiescence or senescence, though most tumors ultimately progress. Preclinical data suggest CDK4/6 inhibition enhances intratumoral inflammation and may synergize with immune checkpoint inhibitors.</p><p><strong>Methods: </strong>This non-randomized, open-label, phase 2 study was conducted at Memorial Sloan Kettering Cancer Center. Patients with metastatic or unresectable DDLPS, or those expected to benefit from systemic therapy prior to surgery, were eligible. Patients received palbociclib (125 mg orally, days 1-21 of a 28-day cycle) plus retifanlimab (500 mg intravenous flat dose every 4 weeks). The primary endpoint was to assess the best objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</p><p><strong>Results: </strong>30 patients were treated and evaluable. Median age was 61 years (range 36-81), 67% were male, and 63% were treatment-naive. The median follow-up was 14.8 months. ORR was 20% (95% CI 8% to 39%) and the clinical benefit rate was 53% (95% CI 34% to 72%). Median progression-free survival and overall survival were 4.8 (95% CI 1.71 to 15.7) and 27 months (95% CI 21.7 to not reached (NR)), respectively. Median duration of response was 18.4 months (95% CI 9.4 months to NR). Grade ≥3 treatment-related adverse events occurred in 61% of patients, including one Grade 4 neutropenia. There were no Grade 5 events. Retifanlimab and palbociclib were discontinued due to toxicity in 23% and 17% of patients, respectively. Tumor sequencing identified <i>JUN</i> amplification in 6 of 14 patients with progressive disease versus 2 patients with stable disease or partial response. Patients with progressive disease had a higher median copy number alteration burden compared with those with stable disease or partial response.</p><p><strong>Conclusions: </strong>Palbociclib plus retifanlimab demonstrated deep and durable responses in a subset of patients with advanced DDLPS, with an ORR exceeding that historically observed with either agent alone. Adverse events were generally manageable. Copy number alteration burden and JUN amplification merit further evaluation as potential biomarkers of resistance.</p><p><strong>Trial registration number: </strong>https://clinicaltrials.gov/study/NCT04438824.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 5","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838123","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":"Phase II trial of combination radiation, hormone, and immunotherapy in grade group 5 prostate cancer.","authors":"John Michael Bryant, Maria Sandoval, Ryan Putney, Purvish Trivedi, Esther N Katende, Angelina Fink, Syeda Mahrukh Naqvi, Youngchul Kim, Vivian Yin, Jingsong Zhang, Jong Y Park, Amparo Serna, Nghi Lam, Julio Pow-Sang, Michael Poch, Roger Li, Brandon J Manley, Arash Naghavi, Javier Torres-Roca, G Daniel Grass, Sungjune Kim, Kujtim Latifi, Dylan Hunt, Peter Johnstone, Jasreman Dhillon, Paulo C Rodriguez, Rohit Jain, Daniel C Fernandez, Kosj Yamoah","doi":"10.1136/jitc-2025-013906","DOIUrl":"https://doi.org/10.1136/jitc-2025-013906","url":null,"abstract":"<p><strong>Background: </strong>Grade group 5 (GG5) prostate cancer (PCa) carries a less favorable prognosis after standard-of-care (SOC) therapy, necessitating novel therapeutic approaches. High-dose rate brachytherapy (HDRBT) and androgen deprivation therapy (ADT) may modulate immune response in GG5 PCa, particularly in tumors with increased immune content. This study evaluated whether the addition of nivolumab to SOC was associated with improved disease control in patients with high-volume GG5 PCa, including those with oligometastatic disease.</p><p><strong>Methods: </strong>In this non-randomized phase II trial, 31 patients with localized or oligometastatic GG5 PCa and >30% positive biopsy cores were evaluated between September 2018 and April 2021. Patients received four doses of nivolumab (240 mg every 2 weeks) beginning 4 weeks prior to HDRBT, alongside ADT, HDRBT, and external beam radiation. The primary endpoint was to evaluate whether the 2-year freedom from biochemical recurrence (FFBR) rate would exceed a prespecified historical control rate of 75%.</p><p><strong>Results: </strong>Among the 31 patients, the median follow-up was 38.8 months (IQR 31.0-46.5 months). The addition of nivolumab to SOC RT with ADT was associated with a 2-year FFBR rate of 90.3% (95% CI 74.3% to 98.0%) (median FFBR not reached), exceeding the prespecified historical control rate of 75% (one-sided p value from binomial test=0.024). Definitive and probable nivolumab-related toxicity included 6.3% acute grade 2 and 6.3% acute grade 3 adverse events (AEs), with no grade 4+ AEs observed. A higher Decipher immunosuppression score at diagnosis correlated with early pathologic response (p=0.005) and was independently associated with time to metastatic failure (p=0.044).</p><p><strong>Conclusions: </strong>Nivolumab combined with SOC was associated with encouraging FFBR in this high-risk GG5 PCa population and may represent a promising therapeutic intensification strategy. The Decipher immunosuppression score may serve as a predictive biomarker for response. These findings warrant further investigation in randomized trials.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 5","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838143","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":"First-in-human use of recombinant IL-7 to potentiate antigen-specific T cell therapy: a single patient case study.","authors":"Casey Bermack, Shailbala Singh, Guangsheng Pei, Sapna P Patel, Linghua Wang, Cassian Yee","doi":"10.1136/jitc-2026-014822","DOIUrl":"10.1136/jitc-2026-014822","url":null,"abstract":"<p><p>Clinical trials of adoptive cellular therapy demonstrate that a key characteristic associated with durable responses is in vivo expansion and persistence of transferred T cells. Strategies to develop a less differentiated, stem/memory population in the infusion product and peri-infusional regimens to promote the maintenance of desired T cell states following adoptive transfer would be desirable. Endogenous T cell therapy studies have routinely achieved memory T cells enriched for expression of interleukin (IL)-7 receptor; to eliminate the conventional requirement for immunosuppressive lymphodepletion and its attendant life-threatening toxicities, we performed the first-in-human use of IL-7 in combination with adoptively transferred antigen-specific memory CD8 T cells in a patient with refractory metastatic uveal melanoma. Single-cell immune repertoire profiling of serial peripheral blood sampling revealed substantial in vivo proliferation and expansion of a stem cell memory population in the endogenous T cell therapy product that achieved a >79% predominance of total circulating T cells by 3 weeks post-infusion in this non-lymphodepleted recipient. Although the patient's disease ultimately progressed, these findings demonstrate safety and proof of concept for an IL-7 treatment regimen for expansion of adoptively transferred T cells in vivo and induced memory differentiation in a heavily pretreated patient with refractory solid malignancy.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 4","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815242","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":"C-type lectin domain family 5 member A-mediated activation of macrophages via a bispecific antibody enhances anti-HER2 therapy.","authors":"Lei Hou, Dechuang Jiao, Hao Dai, Jingyang Zhang, Lina Wang, Xilong Gong, Cuihua Qi, Xuhui Guo, ZhenZhen Liu","doi":"10.1136/jitc-2026-014799","DOIUrl":"10.1136/jitc-2026-014799","url":null,"abstract":"<p><strong>Background: </strong>Although HER2-targeted therapies have dramatically improved outcomes for patients with HER2-positive breast cancer, the immunosuppressive tumor microenvironment remains a major barrier to effective immunotherapy in this subtype. Therefore, we sought to develop a new bispecific antibody targeting both HER2 and C-type lectin domain family 5 member A (CLEC5A), a pattern recognition receptor on innate immune cells like macrophages, aiming to alter the tumor immune environment.</p><p><strong>Methods: </strong>CLEC5A-HER2 bispecific antibodies were generated and evaluated for binding properties, macrophage activation, and phagocytic activity in vitro. Anti-tumor efficacy was assessed in multiple syngeneic mouse models, including orthotopic breast cancer models, with mechanistic studies and immune checkpoint inhibitor combinations.</p><p><strong>Results: </strong>The CLEC5A-HER2 bispecific antibody was more effective in anti-tumor activity than either monotherapies or combinations of individual antibodies in various syngeneic models, including an orthotopic breast cancer model. Mechanistically, it converted \"cold\" tumors into \"hot\" tumors by promoting macrophage-mediated phagocytosis, repolarizing tumor-associated macrophages toward an M1-like phenotype, and enhancing antigen presentation and T-cell recruitment. This immune remodeling restored the CXCL9/10-CXCR3 axis, increased CD8+ T cell infiltration, reduced regulatory T cells, and underpinned a T cell-dependent anti-tumor response. Interestingly, combination therapy with CTLA-4 and PD-1 blockade exhibited strong synergistic effects without significant toxicity.</p><p><strong>Conclusions: </strong>These results identify the CLEC5A-HER2 bispecific antibody as a potential immunotherapy for HER2-positive cancers by effectively engaging both innate and adaptive immunity.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 4","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772074","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":"Immune checkpoint blockade as an accelerator of adrenal aging: a testable model linking low-grade cortical inflammation to proteostasis failure, LDLR/SULT2A1 suppression, and reduced DHEA output.","authors":"Guanxiong Ding, Yangyang Xu, Ting Guo, Chenchen Feng","doi":"10.1136/jitc-2025-014454","DOIUrl":"10.1136/jitc-2025-014454","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) unleashes antitumor immunity but frequently provokes enduring endocrine toxicities. We hypothesize that ICB accelerates adrenal aging by establishing chronic low-level inflammation within the adrenal cortex, with targeting vulnerability of the zona reticularis. Integrating a recently published human multiorgan aging proteome atlas and primate adrenal aging study with survivorship data after ICB therapy, we propose a testable signaling cascade: ICB-amplified interferon gamma (IFNγ)/ tumor necrosis factor (TNF)/ interleukin-1 signaling activates nuclear factor kappa B (NF-κB)/signal transducer and activator of transcription 1 (STAT1), suppressing sterol regulatory element-binding protein 2 (SREBP2)-low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake; concurrent mitochondrial/endoplasmic reticulum stress drives proteome-transcriptome decoupling, loss of cytochrome b5 type A (CYB5A), and impaired cytochrome P450 family 17 subfamily A member 1 (CYP17A1) 17,20-lyase activity; inflammatory transcriptional repression of sulfotransferase family 2A member 1 (SULT2A1) with proteostasis decay reduces dehydroepiandrosterone (DHEA) sulfation. The net result is a persistent fall in DHEA/DHEA sulfate (DHEAS) with comparatively preserved cortisol-mirroring natural adrenal aging. We advocate prospective measurement of DHEAS, DHEA, adrenocorticotropic hormone (ACTH), and cortisol at baseline, during therapy, end of therapy, and 6-24 months post-therapy; if early DHEAS decline is confirmed, targeted interventions including DHEA replacement or glucocorticoid receptor antagonism warrant evaluation. This framework reframes certain endocrine immune-related adverse events as \"accelerated organ aging,\" with implications for risk stratification, toxicity prevention, and survivorship care.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 4","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772093","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":"Enhancing immune response in advanced HCC with PVTT: rivaroxaban as a core adjuvant in combined therapy.","authors":"Ying Yan, Dan Zou, Yifan Li, Huanhuan Ma, Hao Chen","doi":"10.1136/jitc-2025-014060","DOIUrl":"10.1136/jitc-2025-014060","url":null,"abstract":"<p><p>Despite the establishment of combined local and systemic therapy as the standard approach for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), its efficacy remains constrained by two primary challenges: the immunosuppressive tumor microenvironment (TME) and treatment resistance. Recent research shows that factor Xa (FXa) boosts programmed death-ligand 1 (PD-L1) expression in tumor cells via the proteinase-activated receptor-2 (PAR-2) and signal transducer and activator of transcription 2 (STAT2) pathways, aiding immune evasion. Rivaroxaban, an FXa inhibitor, prevents portal vein thrombosis and disrupts the FXa/PAR-2/PD-L1 axis, restoring T cell function. Based on this mechanism, we propose that incorporating rivaroxaban as a core adjuvant into a long-term, 'local-targeted-immune' multimodal strategy can spatiotemporally reprogram the TME in advanced HCC with PVTT. This approach has the potential to effectively overcome treatment resistance and achieve sustained disease control. The hypothesis is readily testable in clinical trials, and if substantiated, it could establish a new treatment paradigm aimed at improving the prognosis for this high-risk patient population. Furthermore, it would provide a robust theoretical rationale and practical guidance for advancing the treatment of advanced HCC with PVTT.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 4","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772082","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":"Aging is associated with the outcomes of immune checkpoint blockade in renal cell carcinoma.","authors":"Zhiyang Huang, Jin Zhou, Zhengrong Zheng, Hong Zhao, Bin Zhao, Rongdong Zeng","doi":"10.1136/jitc-2025-014605","DOIUrl":"https://doi.org/10.1136/jitc-2025-014605","url":null,"abstract":"<p><p>Aging causes gradual and significant declines in immune functions and responses. However, the impact of aging on the immunotherapy outcomes in advanced renal cell carcinoma is largely unknown. Here, we conducted a pooled analysis of individual participant data from two regulatory-approved randomized controlled trials: CheckMate 214 and JAVELIN Renal 101. The overall population (n=1926) included 964 individuals treated with immune checkpoint inhibitors (ICIs) and 962 subjects treated with sunitinib. The optimal age to separate young from old was found to be 60. For young patients, immunotherapy was associated with favorable overall survival (OS; HR=0.70, 95% CI 0.56 to 0.87, p<0.001). For individuals over 60 years old, the OS benefits were marginal (HR=0.82, 95% CI 0.67 to 1.00, p=0.05). Notably, patients with Memorial Sloan Kettering Cancer Center poor risk demonstrated clear benefits from ICIs in this population. Immunotherapy failed to improve OS in patients aged 75 and above (HR=1.05, 95% CI 0.62 to 1.79, p=0.85). Further investigations indicated that young patients exhibited increased infiltration of immune cells, enhanced tumor immunogenicity, and improved immune responses. In summary, the advantage of immunotherapy diminished progressively with age. ICIs were associated with favorable outcomes in young patients. However, for patients over 60 years old, clinicians need to carefully balance efficacy, safety, and patient preferences to deliver individualized treatment.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 4","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772061","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}