Journal for Immunotherapy of Cancer最新文献

{"title":"Comparative clinical outcomes and single-cell profiling of CD19 CAR-T versus blinatumomab for relapsed/refractory B-ALL.","authors":"Kexin Wang, Leijin Yu, Xinghua Liang, Fengmei Song, Songfu Jiang, Shi Han, Mingming Zhang, Kai Liu, Rui Wen, Lele Jin, Yao Xiong, Yunfei Qiu, Huijun Xu, Guoqing Wei, Dongrui Wang, Yongxian Hu, He Huang","doi":"10.1136/jitc-2026-015196","DOIUrl":"10.1136/jitc-2026-015196","url":null,"abstract":"<p><strong>Background: </strong>CD19-targeting chimeric antigen receptor T-cells (CAR-T) and blinatumomab represent two leading immunotherapies for relapsed/refractory B cell acute lymphoblastic leukemia (r/r B-ALL). Despite sharing the same target, their differential clinical efficacy and underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>This retrospective study enrolled 106 r/r B-ALL patients (61 CD19 CAR-T vs 45 blinatumomab) between February 2020 and August 2023. The complete response (CR) rate, long-term survival, and therapeutic toxicities were compared between the two cohorts. Additionally, we conducted scRNA-seq on nine samples of patient-derived CAR-T/ blinatumomab-elicited T cells after infusion and performed a head-to-head comparison in vitro.</p><p><strong>Results: </strong>Overall, the CR or CR with incomplete count recovery (CR/CRi) rate by day 28 after infusion was 96.6% (56/58) in the CAR-T cohort and 77.8% (35/45) in the blinatumomab cohort (p=0.008). With a median follow-up of 10 months (IQR 5.0-19.4), overall survival (OS) and leukemia-free survival (LFS) were comparable. In patients with higher tumor burden (minimal residual disease >20%), CAR-T was associated with a longer LFS (HR 0.453, 95% CI 0.226 to 0.908, p=0.026) compared with blinatumomab. In patients with relapsed disease, CAR-T showed prolonged LFS (HR 0.415, 95% CI 0.221 to 0.778, p=0.006) and a trend toward improved OS (p=0.088). All toxicities were reversible, and any adverse events (AEs) were similar (98.4% vs 88.9%), but severe AEs (grade ≥3) were higher with CAR-T, especially cytokine release syndrome (42.6% vs 13.3%, p<0.001). In addition, scRNA-seq data provided correlative evidence of functional enrichment of effector cells in CAR-T samples during peak expansion at 2 weeks post infusion. Head-to-head comparison in vitro is consistent with the possibility that CAR-T cells may sustain effector function and cytotoxicity following tumor engagement, whereas blinatumomab-elicited T cells tended to show relatively higher exhaustion and reduced cell recovery.</p><p><strong>Conclusions: </strong>Our findings suggest that CD19 CAR-T therapy is associated with a higher CR/CRi rate compared with blinatumomab, particularly in patients with high tumor burden and relapsed disease, despite a higher severe toxicity profile.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074698","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":"Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer.","authors":"Anmbreen Jamroze, Renyuan Zhang, Emily Dougherty, Kriti Ahuja, Lei Deng, Karan Jatwani, Uyen V Nguyen, Bailey Farmer, Gaybrielle James, Michalis Mastri, Kevin H Eng, Bo Xu, Yvonne Saenger, Yuanquan Yang, John J Krolewski, Dean G Tang, Gurkamal Chatta, Kent L Nastiuk","doi":"10.1136/jitc-2026-015348","DOIUrl":"10.1136/jitc-2026-015348","url":null,"abstract":"<p><strong>Background: </strong>Novel therapies to prevent lethal castration-resistant prostate cancer in response to standard-of-care androgen deprivation therapy (ADT) are required. Unfortunately, most prostate cancers are \"immune cold\" and fail to respond to checkpoint inhibitors (CPIs). To assess whether ADT induces changes that enable more effective CPI therapy, we examined the tumor immune microenvironment (TiME) following neoadjuvant ADT (nADT).</p><p><strong>Methods: </strong>Radical prostatectomy specimens from 43 nADT-treated patients were stratified into three duration groups and compared with each other and with matched controls. RNA sequencing and quantitative multispectral immunofluorescence (qmIF) staining were performed to analyze transcriptomic and TiME abundance and cellular spatial relationship differences after nADT.</p><p><strong>Results: </strong>Immune and inflammatory pathways, particularly of antigen presentation and adaptive immune response, were increased, most notably in tumors receiving 3-5 months nADT. qmIF revealed a complex temporal response in the TiME, with a dramatic influx of cytotoxic T lymphocytes (CTLs) and T-helper cells after 3-5 months of nADT. However, after 6 months nADT, M2-like tumor-associated macrophages (TAMs) and regulatory T cells were strikingly increased while CTLs decreased. Spatially, CTLs and T-helper cells clustered near tumor cells at 3-5 months nADT, but were replaced by M2-TAMs in tumors receiving ≥6 months of nADT.</p><p><strong>Conclusions: </strong>These data reveal the induction of a bi-phasic response in the TiME: robust CTL activation 3-5 months after nADT is initiated, followed by myeloid immunosuppression in tumors receiving prolonged nADT. This ADT-induced reprogramming of the TiME suggests a critical window of opportunity where short-duration ADT might augment CPI efficacy, converting cold into immunologically responsive tumors.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074832","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":"Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer.","authors":"Charu Aggarwal, Daniel Sterman, Jessica Dwyer, Erin R Alesi, Fabien Maldonado, Ranee Mehra, Christine Bestvina, Janani Reisenauer, Shiven Patel, Omar Ibrahim, George Eapen, William Guesdon, Matthew Wai Heng Chung, Caroline Duault, Mina Rohani Pichavant, Sacha Gnjatic, Seunghee Kim-Schulze, Holden T Maecker, Anne R Diers, Qiuchen Guo, Garrett Nichols, Andrea Manzanera, Francesca Barone, Paul P Tak","doi":"10.1136/jitc-2026-015821","DOIUrl":"10.1136/jitc-2026-015821","url":null,"abstract":"<p><strong>Background: </strong>Patients with advanced non-small cell lung cancer who progress on immune checkpoint inhibitors (ICIs) face limited options and poor survival. Aglatimagene besadenovec (CAN-2409), a replication-defective adenoviral vector encoding herpes simplex virus-thymidine kinase, plus valacyclovir, has been shown to induce immunogenic cell death and systemic immune activation.</p><p><strong>Methods: </strong>In this open-label, phase 2a clinical trial, 76 patients were enrolled (intention-to-treat population) and 73 received at least one dose of aglatimagene besadenovec (safety population); 46 patients who received two intratumoral aglatimagene besadenovec injections, completed protocol-defined valacyclovir exposure, and underwent a 12-week imaging comprised the evaluable (per-protocol) population. Endpoints included clinical and immunological outcomes.</p><p><strong>Results: </strong>In the 73 patients included in the safety analysis (including patients who did not receive a second injection due to apparent pseudoprogression), median OS was 14.3 months. In the evaluable (per-protocol) population of 46 patients who completed protocol-defined treatment and week-12 imaging, median OS was 24.5 months (95% CI 16.0 to 33.8). Among the 41 evaluable patients in cohort 2, 15 (37%) were alive at ≥24 months and 5 (12%) at ≥40 months. In the 46-patient evaluable population, the objective response rate was 10.9% (5/46; 95% CI 4.7% to 23.0%) and the disease control rate was 71.7% (33/46; 95% CI 57.5% to 82.7%). In the 73 patients included in the safety analysis (including patients who did not receive a second injection due to apparent pseudoprogression) median overall survival was 14.3 months. Exploratory biomarkers demonstrated systemic immune reactivation, including cytotoxic T-cell expansion and regression of uninjected lesions, with stronger signals in non-squamous histology. No grade 4 treatment-related adverse events or treatment-related deaths were reported. Most treatment-related adverse events were grade 1-2; 10/73 patients (13.7%) experienced grade 3 treatment-related adverse events. Six patients discontinued because of adverse events, including two with events considered possibly related to treatment (including ongoing ICI).</p><p><strong>Conclusions: </strong>In this single-arm phase 2a study, aglatimagene besadenovec plus valacyclovir with ongoing ICI was associated with systemic immune remodeling and encouraging survival. Because comparisons with historical controls are descriptive and vulnerable to selection and other biases, efficacy requires confirmation in a randomized controlled clinical trial, which has been initiated.</p><p><strong>Trial registration number: </strong>NCT04495153.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074760","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":"IL-23-engineered oncolytic vaccinia virus enhances pancreatic cancer control through inflammasome-driven Th17-skewed CD4⁺ T-cell responses.","authors":"Yu Guo, Meng Wang, Yujing Xuan, Lvla Pan, Wenyi Yan, Jisiyu Cheng, Yang Yu, Xiangyu Wang, Lihua Xu, Xianlei Sun, Ruxia Han, Lingling Si, Yaohe Wang, Sirui Li, Pengju Wang","doi":"10.1136/jitc-2026-016326","DOIUrl":"10.1136/jitc-2026-016326","url":null,"abstract":"<p><strong>Background: </strong>Oncolytic viruses represent a promising immunotherapeutic strategy for converting pancreatic and other immunologically cold tumors. While their ability to stimulate innate immune signaling and promote antitumor immunity is established, mechanisms enabling durable adaptive responses remain poorly defined.</p><p><strong>Methods: </strong>We used CRISPR-Cas9-based homologous recombination to generate a thymidine kinase (TK) and B2R double-deleted backbone virus, VV∆TK∆B2R (VV-DD). On this backbone, we engineered VV∆TKmp40∆B2Rmp19 (VV-DDIL23), which expresses the p40 and p19 subunits of interleukin-23 (IL-23) separately to mimic natural heterodimer assembly. Its antitumor efficacy was evaluated in immunosuppressive pancreatic ductal adenocarcinoma models and compared with a single-chain IL-23 fusion construct (VV-DDIL23F). In parallel, unbiased single-cell RNA sequencing was employed to systematically dissect the immune mechanisms underlying the potent antitumor activity of VV-DDIL23.</p><p><strong>Results: </strong>VV-DDIL23 exhibited potent antitumor efficacy and significantly outperformed VV-DDIL23F. Single-cell RNA sequencing revealed that VV-DDIL23 enhanced antigen processing and presentation in macrophages, characterized by elevated major histocompatibility complex-II expression, upregulation of co-stimulatory molecules, and production of cytokines including interferon-I and IL-1β. This was accompanied by the emergence of a distinct population of tumor-infiltrating CD4⁺ T cells that mediated long-term memory immune surveillance against tumors. Mechanistically, VV-DDIL23 infection triggered tumor cell-mediated activation of the macrophage inflammasome, leading to IL-1β release. Notably, IL-1β synergized with virally encoded IL-23 to promote the differentiation of Th17-skewed Cxcr6⁺Rora⁺ CD4⁺ T cells with sustained antitumor functions.</p><p><strong>Conclusion: </strong>This work reveals a previously unrecognized pathway linking innate viral recognition by macrophages to CD4⁺ T cell-directed differentiation and tumor clearance, providing a novel therapeutic strategy to overcome immunosuppression in pancreatic cancer.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074826","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":"METLUNG: plasma metabolomic profiling identifies metabolomic signatures associated with immunotherapy outcomes in non-small cell lung cancer.","authors":"Clara Lucía-Gozálvez, Christopher Papandreou, Joan Badia, Raquel Cumeras, Sergio Peralta, Cristina Martí, Ana Vidaller, Laura Quintana, Salvador Martínez, Josep Gumà","doi":"10.1136/jitc-2026-016077","DOIUrl":"10.1136/jitc-2026-016077","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Identifying reproducible biomarkers associated with treatment outcomes remains a major unmet clinical need in advanced non-small cell lung cancer (NSCLC). METLUNG evaluated whether plasma metabolomic profiling, alone or combined with clinical variables, could identify biomarkers associated with clinical response and survival outcomes in patients with NSCLC treated with immune checkpoint inhibitors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;METLUNG is a prospective observational cohort (ISRCTN98848959) that enrolled 128 patients with stage III-IV NSCLC eligible for immune checkpoint inhibitors between October 2020 and December 2022 at Hospital Universitari Sant Joan de Reus, Reus (Spain). Clinical response classification was based on Immune Response Evaluation Criteria in Solid Tumors criteria, and subsequent clinical and radiological course. Baseline plasma metabolomic profiling was followed by univariate analyses and multivariate modeling. Survival models were built using clinical variables, metabolomic variables, significant metabolites, and an integrated clinical-metabolomic composite model. Predictive performance was evaluated using integrated area under the receiver operating characteristic curve and concordance index (C-index).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 127 evaluable patients, 52.8% achieved a clinical response. Most had adenocarcinoma (n=94), followed by squamous carcinoma (n=28). Treatment included first-line immunotherapy monotherapy (n=39), first-line chemo-immunotherapy (n=47), or second-line immunotherapy (n=41). Clinical response differed by sex and Eastern Cooperative Oncology Group performance status but showed no association with smoking history or PD-L1 expression.Univariate analyses identified 41 baseline metabolites associated with response, and 69 and 71 metabolites associated with progression-free survival and overall survival (OS), respectively. Five metabolites (histidine, citric acid, uracil, lactic acid, and sarcosine) remained consistently significant across all endpoints. Higher histidine and citric acid levels were associated with improved outcomes, whereas uracil, lactic acid, and sarcosine correlated with worse outcomes. The integrated clinical-metabolomic model showed the highest prognostic performance compared with clinical or metabolomic prognostic models alone, providing better early survival discrimination. In the immunotherapy monotherapy subgroup, only the integrated model was significant for OS, while metabolomic signatures showed stronger prognostic value.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Metabolomic profiling identified metabolic signatures associated with clinical response and survival outcomes in NSCLC patients treated with immune checkpoint inhibitors. An integrated clinical-metabolomic model showed improved prognostic stratification, supporting the potential value of plasma metabolomics for patient risk stratification. These findings remain exploratory and require va","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061365","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":"Toward precision adjuvant immunotherapy in high-risk clear cell renal cell carcinoma: integrating plasma multiomics with PD-1 blockade.","authors":"Rakesh Kumar, Duminduni Hewa Angappulige, Jianxun Song","doi":"10.1136/jitc-2026-016587","DOIUrl":"10.1136/jitc-2026-016587","url":null,"abstract":"<p><p>Despite curative-intent nephrectomy, approximately one-third of patients with localized clear cell renal cell carcinoma (ccRCC) eventually experience disease recurrence due to occult minimal residual disease. Although adjuvant immune checkpoint blockade has transformed postoperative management for patients at high risk of relapse, clinical benefit remains heterogeneous, underscoring the need for biomarkers capable of identifying individuals most likely to benefit from treatment. In this issue of the <i>Journal for ImmunoTherapy of Cancer</i>, Wang <i>et al</i> report a prospective, multicenter, non-randomized phase II trial evaluating adjuvant penpulimab in patients with very-high-risk ccRCC following nephrectomy. Beyond demonstrating improved disease-free survival compared with surveillance, the investigators integrated plasma proteomic and metabolomic analyses to identify circulating immune-metabolic signatures associated with recurrence. This study extends the discussion of adjuvant immunotherapy beyond demonstrating efficacy toward understanding biological heterogeneity, and developing biomarker-guided treatment strategies. Although the non-randomized design, limited sample size, and exploratory biomarker analyses preclude immediate changes to clinical practice, the study highlights the promise of combining prospective immunotherapy trials with liquid biopsy-based multiomics. Such approaches may ultimately enable precision adjuvant immunotherapy by improving postoperative risk stratification, monitoring minimal residual disease, and guiding individualized treatment decisions in patients with high-risk ccRCC.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038818","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":"AdvanTIG-105: a phase I/Ib dose-expansion study of ociperlimab plus tislelizumab with or without chemotherapy in metastatic non-small cell lung cancer and extensive-stage small cell lung cancer.","authors":"Shun Lu, Yan Yu, Jun Zhang, Qiming Wang, Eun Kyung Cho, Jun Zhao, Se Hyun Kim, Youngjoo Lee, Timothy D Clay, Tsung-Ying Yang, Gee-Chen Chang, Haiyuan Yang, Yunxia Zuo, Rui Liu, Pu Sun, Hye Ryun Kim","doi":"10.1136/jitc-2026-015474","DOIUrl":"10.1136/jitc-2026-015474","url":null,"abstract":"<p><strong>Background: </strong>Patients with metastatic non-small cell lung cancer (NSCLC) or extensive-stage small cell lung cancer (ES-SCLC) have poor prognosis and survival with current standard of care. Several checkpoint inhibitor combinations have been evaluated clinically. We report outcomes from the dose-expansion cohorts of patients with NSCLC or ES-SCLC from the AdvanTIG-105 clinical trial.</p><p><strong>Methods: </strong>AdvanTIG-105 was a phase I/Ib, open-label, multicenter clinical trial of ociperlimab plus tislelizumab with or without chemotherapy in patients with unresectable locally advanced or metastatic solid tumors, including NSCLC and ES-SCLC (NCT04047862). The dose-expansion cohorts received ociperlimab (anti-T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domain) 900 mg intravenously and tislelizumab (anti-programmed cell death-protein 1) 200 mg intravenously every 3 weeks (Q3W) ± chemotherapy for four cycles, followed by ociperlimab 900 mg intravenously and tislelizumab 200 mg intravenously Q3W. The primary endpoint was the objective response rate. Other key endpoints included duration of response and safety.</p><p><strong>Results: </strong>As of August 7, 2024, patients with untreated squamous NSCLC (sqNSCLC; n=41), untreated non-sqNSCLC (n=43), untreated programmed cell death-ligand 1+ NSCLC (tumor cell ≥1%; n=45), checkpoint inhibitor-experienced NSCLC (n=26), and untreated ES-SCLC (n=43) were treated in the dose-expansion phase; of these, 40, 42, 45, 26, and 41 patients, respectively, were efficacy evaluable. ORR (95% CI) was 55.0% (38.5% to 70.7%), 54.8% (38.7% to 70.2%), 40.0% (25.7% to 55.7%), 7.7% (0.9% to 25.1%), and 65.9% (49.4% to 79.9%), respectively. Median (95% CI) DOR was 16.9 (5.6 to not estimable (NE)), 13.9 (8.2 to NE), 14.0 (2.9 to NE), 15.9 (12.6 to NE), and 4.1 (3.4 to 5.6) months, respectively. Median (95% CI) progression-free survival was 8.2 (6.0 to 18.1), 11.3 (8.0 to 20.7), 5.5 (4.2 to 8.2), 2.9 (1.4 to 5.3), and 4.9 (4.2 to 5.5) months, respectively. Treatment-related treatment-emergent adverse events (TR-TEAEs) were experienced by 39 (95.1%), 41 (95.3%), 38 (84.4%), 19 (73.1), and 39 (90.7%) patients, respectively, with 24 (58.5%), 26 (60.5%), 9 (20.0%), 6 (23.1%), and 23 (53.5%) experiencing Grade 3-4 TR-TEAEs.</p><p><strong>Conclusions: </strong>Ociperlimab and tislelizumab±chemotherapy demonstrated a manageable safety profile and preliminary antitumor activity in patients with NSCLC or ES-SCLC. Findings from this small phase I study should be interpreted with caution.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149038836","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":"Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.","authors":"Jie-Tao Ma, Li Sun, Ling-Yun Zhang, Le-Tian Huang, Shu-Ling Zhang, Nan Sun, Yu-Yang Dong, Xiao-Han Li, Yong Yue, Mei-Qi Yang, Jia-Yuan Jiang, Jin Feng, Xue Han, Yu-Ting Wu, Shi-Wei Wang, Yu-Ting Jiang, Shi-Tong Guan, Xue-Mei Chen, Cheng-Bo Han","doi":"10.1136/jitc-2026-016280","DOIUrl":"10.1136/jitc-2026-016280","url":null,"abstract":"<p><p>Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4⁺/CD8⁺ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4⁺/CD8⁺ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4⁺/CD8⁺ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.<b>Trial registration number</b>ChiCTR2400094398.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030647","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":"SPP1⁺ macrophage-induced CD74⁺ tumor cells promote adrenocortical carcinoma tumor thrombus via the SPP1/CD44/JAK/STAT signaling.","authors":"Houliang Zhang, Kangjie Xu, Lan Zhen, Yanji Jiang, Anyang Chou, Ming Chen, Yu Chen, Jianping Wu, Weipu Mao","doi":"10.1136/jitc-2026-015080","DOIUrl":"10.1136/jitc-2026-015080","url":null,"abstract":"<p><p>Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy with limited treatment options and poor prognosis. Venous tumor thrombus (VTT) is a common complication associated with ACC progression, yet the cellular and molecular mechanisms driving VTT formation remain largely unknown. We performed integrated single-cell RNA sequencing and spatial transcriptomics on paired samples of primary tumor, VTT tail, and VTT head obtained from one ACC patient, followed by in vitro and in vivo functional validation. Our results identified a distinct CD74⁺ tumor cell subcluster enriched in the VTT head region, and functional assays demonstrated that CD74 significantly enhances ACC cell migration, invasion, and proliferation through activation of the JAK-STAT signaling pathway. Moreover, spatial and ligand-receptor analyses revealed that SPP1⁺ macrophages closely interact with CD74⁺ tumor cells via the SPP1-CD44 axis. Functional experiments confirmed that SPP1 secreted by macrophages potentiates CD74-induced JAK-STAT activation and malignant phenotypes. Collectively, we found that CD74⁺ tumor cells drive ACC progression under the regulation of the SPP1-CD44 signaling pathway in the vicinity of SPP1⁺ macrophages, thereby revealing a novel mechanistic axis with therapeutic potential.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030750","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":"Intravenously deliverable oncolytic virus VET3-TGI favorably alters the tumor microenvironment.","authors":"Ming Zhang, Katy Barrett, Carly Carter, Padma Sampath, Gabriella Acosta-Barreto, Sydney Audino, Jirapach Moongdee, Rachel Bouchard, Deanna Dunstane, Nick Matteo, Kyle Biery, Evalien Duyvesteyn, Monica Cantos, Kimberly M Brothers, Dan Byrd, Taylor Dietrich, Ravikumar Muthuswamy, Stephen H Thorne","doi":"10.1136/jitc-2026-015643","DOIUrl":"10.1136/jitc-2026-015643","url":null,"abstract":"<p><strong>Background: </strong>Oncolytic viruses have pledged to combat cancer by causing immunogenic cell death of cancerous cells while priming cancer-specific immune responses. These outcomes have proven elusive in the clinic. Current-generation vectors rarely reach effective concentrations inside tumors when given intravenously, and consequently are limited to intratumoral administration. Even after direct tumor infusion, these therapies frequently fail to overcome local immunosuppression caused by inappropriate activation of transforming growth factor beta (TGF-β) signaling throughout the tumor microenvironment.</p><p><strong>Methods: </strong>VET3-TGI is a vaccinia virus that expresses the chemokine receptor C-X-C chemokine receptor 3 (CXCR3) in infected cells within the first hours after infection. Circulating cells infected in situ on intravenous infusion are driven to migrate to tumors that express cognate chemokines, thus delivering the virus to its target. Infected tumor cells subsequently secrete interleukin-12 (IL-12) and a soluble TGF-β inhibitor.</p><p><strong>Results: </strong>Expression of CXCR3 from vaccinia virus boosted delivery of virus to tumors containing C-X-C motif chemokine 9 and C-X-C motif chemokine 10, which are known to be upregulated in many human cancers. VET3-TGI effectively combated tumor growth when administered intravenously as a single agent in multiple mouse tumor models. In these models, IL-12 provoked inflammation-driven antitumor activity from immune cells. This activity was strengthened by local TGF-β blockade, which crippled the ability of tumors to suppress the immune response.</p><p><strong>Conclusions: </strong>VET3-TGI demonstrates the efficacy of three different transgenes with distinct and complementary activities: CXCR3 for tumor targeting to enable intravenous delivery, a TGF-β inhibitor to disrupt immunosuppression, and IL-12 to promote antitumor immunity.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"14 9","pages":""},"PeriodicalIF":11.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017005","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}