Cancer immunology, immunotherapy : CII最新文献

{"title":"Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.","authors":"Mahsa Fatahichegeni, Mohammad Amin Ansarian, Mi Xiao, Wenjuan Gao, Ruiming Shi","doi":"10.1007/s00262-026-04384-1","DOIUrl":"10.1007/s00262-026-04384-1","url":null,"abstract":"<p><p>Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responses in molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694732","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 Blimp-1 in T cells results in activation of T-bet-mediated control of immunosuppression in lung cancer.","authors":"Susetta Finotto, Mircea T Chiriac, Susanne Krammer, Zuqin Yang, Laura Neurath, Carol I Geppert, Elvedina Nendel, Sonja Trump, Adriana Geiger, Stefan Wirtz, Sebastian Zundler, Markus F Neurath","doi":"10.1007/s00262-026-04381-4","DOIUrl":"10.1007/s00262-026-04381-4","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer-related death in the world. Blimp-1 is a transcriptional repressor that, by interacting with other transcription factors in lymphocytes, regulates their cellular fate.</p><p><strong>Objective: </strong>In this study, we focused on the role of Blimp-1 in T cells in lung cancer.</p><p><strong>Methods: </strong>Here, we analyzed, in a murine model of NSCLC, the role of Blimp-1 in T cells after targeting Blimp-1 in T cells expressing lymphocyte-specific-protein tyrosine kinase (Lck), a kinase crucial for T-cell receptor signaling.</p><p><strong>Results: </strong>We found that mice lacking Blimp1 expression in T cells have reduced lung tumor load, suppressed lung Foxp3+Treg cells in the lung and draining lymph nodes, and induced T-bet+CD4+T effector cells producing IFN-gamma and interleukin-2. Furthermore, RNA sequencing of spleen CD4+T cells showed an induction of Th1 markers, including TNF, IL-2 and interferon type I-related genes, but also PD1. RNA sequencing of spleen CD8+T cells showed induced Tc1 markers, including IL12rb1, CD44, granzyme M and eomesodermin, in the absence of Blimp1. Finally, in the lung of mice with Blimp1 deficiency in T cells, we found an upregulation of CD8+T cells with increased release of cytotoxic mediators able to induce lung tumor cell death.</p><p><strong>Conclusions: </strong>These data indicate that the tumor microenvironment induces Blimp-1 in immunosuppressive Treg and T effector cells, thereby limiting the therapeutic efficacy of anti-tumor immune responses. Targeting of Blimp-1 in T cells emerges as a novel concept to suppress immune evasion in lung cancer by regulating CD4+, CD8+and Treg function in the lung.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694735","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":"Hematological toxicities and thrombosis risk associated with immune checkpoint inhibitors: a pharmacovigilance study from 2014 to 2024.","authors":"Jingyi Hou, Guangyan Mu, Zhuo Zhang, Qian Xiang, Yimin Cui","doi":"10.1007/s00262-026-04380-5","DOIUrl":"10.1007/s00262-026-04380-5","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in a wide range of cancers but may also induce hematological toxicities and thrombosis risk. This study comprehensively evaluated hematological and thrombotic adverse events (AEs) associated with ICIs in real-world settings using the FDA Adverse Event Reporting System (FAERS) database, aiming to characterize their clinical features.</p><p><strong>Methods: </strong>Data were extracted from the FAERS database (Q1 2014 to Q4 2024) for disproportionality analysis. AEs were classified using the Medical Dictionary for Regulatory Activities (MedDRA). Associations between ICIs and hematological/thrombotic AEs were assessed via the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) methods. Clinical characteristics of affected patients were analyzed, and time-to-onset across ICI regimens was further evaluated.</p><p><strong>Results: </strong>We identified 14,753 ICI-associated hematological toxicities and thrombotic events. Among reports with available sex information, a higher reporting frequency was observed in men (50.90%) than in women (40.11%). The most frequent AEs were anemia (2963 cases, 16.62%), thrombocytopenia (1961, 11.00%), febrile neutropenia (1935, 10.85%), neutropenia (1392, 7.81%), myelosuppression (979, 5.49%), pancytopenia (739, 4.14%), lymphadenopathy (475, 2.66%), disseminated intravascular coagulation (DIC; 468, 2.62%), leukopenia (468, 2.62%), and deep vein thrombosis (DVT; 213, 1.19%). The median time-to-onset for ICI monotherapy-associated AEs was 28 days (IQR 11-79), with 78.22% occurring within 3 months. Notably, DIC and DVT had the highest mortality proportion among the top 10 AEs.</p><p><strong>Conclusion: </strong>Hematological and thrombotic AEs associated with ICI therapy show notable reporting frequencies in FAERS. Combination regimens demonstrated stronger reporting signals for certain events. These AEs frequently showed early reporting and notable mortality proportions, highlighting the importance of clinical vigilance. Further studies are needed to confirm these findings.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694744","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":"Promoting APC function of B cells via reprogramming the fatty acid metabolism enhances anticancer immunity in metastatic ovarian cancer.","authors":"Haoke Zhang, Chunyan Yu, Wei Du, Huiyang Li, Zihe Liu, Xueying Li, Yuhan Yue, Bo Wang, Hongmei Wang, Yuqing Ouyang, Haixia Wu, Xiaofan Feng, Jianchun Yu, Yaru Liu, Boyu Ji, Siyu Cai, Hong Zhang, Weimin Deng","doi":"10.1007/s00262-026-04387-y","DOIUrl":"10.1007/s00262-026-04387-y","url":null,"abstract":"<p><p>B cells have become one of the important participants in anti-tumor immunity. Compared with DCs and macrophages, B cells have unique advantages in presenting low-abundance antigens to T cells. Fatty acids play a key role in the metabolic adaptation of B cells. Whether the APC function of B cells can be enhanced through reprogramming fatty acid metabolism in the tumor microenvironment (TME) is worthy of study. Ovarian cancer (OvCa) is a gynecological malignant tumor with a high mortality rate. Most patients in the advanced stage often have extensive omental metastasis and ascites formation, which are rich in adipocytes and fatty acids. Given reasons including complex TME, the clinical efficacy of new immunotherapies such as immune checkpoint blockade (ICB) therapy for OvCa is very limited. Therefore, treatment regimens based on new mechanisms are urgently needed to be developed. In this study, we applied the Gene Expression Omnibus (GEO) database, clinical specimens, cell lines, and mouse models to investigate whether reprogramming the fatty acid metabolism in B cells could enhance their APC function and to explore the underlying mechanisms. We also evaluated the therapeutic effects of the combined treatment using APC-enhanced-B cells adoption with low-dose chemotherapy in metastatic OvCa mice. Our research provides new clues forB cells-based anti-tumor immunotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694739","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":"Radiation-induced remodeling of the T cell landscape in head and neck cancer.","authors":"Abdullah A Memon, Imaad Said, Ean Norenberg, Anne Frei, Jamie Foeckler, Fumou Sun, Michael B Dwinell, Robert B Lochhead, Jennifer Bruening, Kenneth Akakpo, Becky Massey, Stuart J Wong, Peiman Hematti, Tyce J Kearl, Musaddiq J Awan, Heather A Himburg, Joseph Zenga","doi":"10.1007/s00262-026-04389-w","DOIUrl":"10.1007/s00262-026-04389-w","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with high recurrence rates and substantial treatment-related morbidity. Radiation therapy remains a central component of the management of locoregional disease. Although radiation directly damages malignant cells through DNA breaks and associated stress pathways, radioresistance remains common, and a proportion of patients continue to develop locoregional recurrence or distant metastasis despite adequate locoregional control. Recent advances in single-cell and spatiotemporal profiling of HNSCC have clarified how radiation alters systemic and intra-tumoral T cell populations and produces a post-radiation tumor microenvironment that provides insufficient support for the robust priming of new tumor-reactive responses. These insights help explain why clinical trials combining radiotherapy with immune checkpoint inhibitors have not reproduced the synergy predicted by preclinical models. At the same time, they point to opportunities to design radiation as a programmable immune adjuvant. In this review, we summarize emerging mechanistic data on radiation-induced remodeling of the T cell landscape, outline the barriers that limit productive immune priming after treatment, and discuss strategies aimed at restoring effective anti-tumor immunity in the post-radiation setting.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694798","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":"A phase I, single-arm, open-label, dose-escalation, multicenter study of SAR445419, an off-the-shelf, ex vivo expanded allogeneic natural killer cell product, in participants with relapsed or refractory acute myeloid leukemia.","authors":"Marina Konopleva, Vijaya Raj Bhatt, Ioannis Mantzaris, Abhishek Maiti, Krishna Gundabolu, Jolie Schafer, Kyle Jensen, Rao Saleem, Yi Li, Agata Drewniak, Pierre Bay, Winston Huh, Ozlem Yildirim, Giovanni Abbadessa, Sarah Cooley, Naval Daver","doi":"10.1007/s00262-026-04333-y","DOIUrl":"10.1007/s00262-026-04333-y","url":null,"abstract":"<p><strong>Background: </strong>SAR445419 is an investigational, off-the-shelf, allogeneic NK cell therapy derived from donor peripheral blood mononuclear cells and expanded ex vivo using PM21 particles.</p><p><strong>Methods: </strong>This multicenter, Phase 1, dose-escalation study (NCT05712278) evaluated optimal dose(s), safety, and tolerability of SAR445419 in adults (aged ≥ 18 years) with relapsed/refractory acute myeloid leukemia (R/R AML). Following lymphodepleting chemotherapy (fludarabine 30 mg/m²/day and cytarabine 2 g/m²/day for 5 days), participants received six intravenous SAR445419 (1 × 10⁹ and 3 × 10⁹ NK cells/dose) doses, starting with the lower dose. The primary endpoint was the incidence of dose-limiting toxicities (DLTs), and key secondary endpoints included adverse events (AEs), hematological recovery, hematopoietic stem cell transplantation, and response rate.</p><p><strong>Results: </strong>Of the 12 planned participants, 7 patients were enrolled, of whom 6 received SAR445419 before sponsor decided early study termination for reasons unrelated to safety or efficacy. No DLTs were observed. All participants experienced treatment-emergent adverse events (TEAEs); six had grade ≥ 3 TEAEs; and four had serious adverse events (SAEs). Two SAR445419-related SAEs (infusion-related reactions: both grade 2) were managed with supportive care. All participants experienced grade 3 anemia and grade 4 thrombocytopenia and neutropenia. Five deaths were reported, all due to disease progression, none related to SAR445419. No clinical responses were observed.</p><p><strong>Conclusions: </strong>This study demonstrated the overall safety of off-the-shelf ex vivo expanded allogeneic NK cells in patients with R/R AML. The successful manufacturing and distribution support the feasibility of donor-derived off-the-shelf NK cells in a clinical setting. Further investigations are required to improve the clinical efficiency of NK cells.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655105","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 the COX-2/PGE₂ axis to enhance NK and T cell immunotherapy in brain tumors.","authors":"Chih-Jie Shen, Joy Florentino-Krasnov, You-Cheng Liao, Hong-Wen Tang, Bahagia Willibrordus Maria Nainggolan, Yung-Hsiao Chiang, Tsung-I Hsu","doi":"10.1007/s00262-026-04372-5","DOIUrl":"10.1007/s00262-026-04372-5","url":null,"abstract":"<p><p>Aggressive brain tumors such as glioblastoma (GBM) remain among the most lethal human cancers, with a median survival of only 15 months despite multimodal treatment. Their resistance arises from a triad of barriers-the blood-brain barrier (BBB), marked intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment (TME). Immunotherapeutic strategies based on natural killer (NK) and T cells, leveraging antigen-independent cytotoxicity and antigen-specific precision, respectively, offer potential breakthroughs but are often limited by chronic neuroinflammation. A key driver of TME suppression is prostaglandin E2 (PGE2), produced via the cyclooxygenase-2 (COX-2) pathway. PGE2 exerts a dual role: Intracellularly, it can promote apoptosis, whereas extracellularly, it fosters tumor progression, immune evasion, and therapeutic resistance. Through activation of EP2 and EP4 receptors, PGE2 signals via Gαs proteins to elevate cyclic adenosine monophosphate (cAMP), leading to impaired cytotoxic immunity. This signaling downregulates NK cell activating receptors (e.g., NKG2D, NKp30), induces CD8⁺ T cell exhaustion, and promotes regulatory T cell expansion. The COX-2/PGE₂ axis further mediates resistance to checkpoint inhibitors, CAR-T therapy, and chemotherapy by enhancing neuronal excitation through EP1 receptor activation in GBM. Targeting this pathway has therefore emerged as a compelling therapeutic strategy, which can restore NK and T cell function and sensitize tumors to immunotherapy. Combining PGE₂ modulation with next-generation NK/T cell approaches-including CAR-NK and CAR-T platforms-holds promise to overcome immune resistance and redefine therapeutic paradigms for GBM and other central nervous system malignancies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648833","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 ST3GAL1 to downregulate ligands for the glycoimmune checkpoint Siglec-7 and reverse immune escape in hepatocellular carcinoma.","authors":"Tan-Chi Fan, Tsai-Hsien Hung, Chau-Ting Yeh, Po-Ting Lin, Nai-Chuan Chang, Tzu-Chi Lo, Tsai-Jung Wu, John Yu, Alice L Yu","doi":"10.1007/s00262-026-04388-x","DOIUrl":"10.1007/s00262-026-04388-x","url":null,"abstract":"<p><p>Sorafenib is the first-line therapy for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib remains a significant challenge. Previous studies have shown that sorafenib treatment induces the formation of truncated O-glycans in HCC cells, but the relationship between sorafenib-induced glycosylation changes and acquired therapy resistance remains unclear. Primary natural killer (NK) cells, freshly isolated from peripheral blood or following culture and expansion, expressed the glycoimmune checkpoints Siglec-7 and Siglec-9. HCC cells exhibited varying levels of Siglec-7/9 ligands on their surface. Sorafenib-resistant liver cancer cells displayed hypersialylation, leading to increased expression of surface Siglec-7/9 ligands, which conferred protection against NK cell-mediated cytotoxicity. Silencing ST3GAL1 significantly reduced Siglec-7 ligand expression on liver cancer cells, enhancing their susceptibility to NK-mediated cytotoxicity and cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) in epidermal growth factor receptor (EGFR)-expressing tumor cells. Furthermore, high ST3GAL1 expression correlated with poor clinical outcomes in patients with stage 1-2 HCC. This study highlights the critical role of ST3GAL1 in regulating Siglec-7 ligands to facilitate immune escape from NK cell cytotoxicity. Moreover, its elevated expression is associated with adverse clinical outcomes in HCC. Targeting ST3GAL1 may represent a promising strategy to enhance NK cell-mediated anti-tumor immunity in HCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648709","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":"Comparative safety of PD-1 and PD-L1 inhibitors in advanced solid tumors: a real-world cohort study with competing risk analysis.","authors":"Yu-Hsiang Shih, Shao-Jing Wang, Chun-Ting Fan, Ting-Fang Lu, Yen-Fu Chen, Lou Sun, Shih-Tien Hsu, Jenn-Jhy Tseng, Chien-Hsing Lu","doi":"10.1007/s00262-026-04379-y","DOIUrl":"10.1007/s00262-026-04379-y","url":null,"abstract":"<p><strong>Background: </strong>Real-world evidence comparing long-term safety between PD-1 and PD-L1 inhibitors is limited, and the impact of competing mortality is unclear.</p><p><strong>Methods: </strong>This retrospective cohort study utilized the TriNetX platform (2014-2024). Adults with advanced solid tumors initiating a PD-1 or PD-L1 inhibitor within 3 months of diagnosis were included. A 1:1 propensity score match created balanced cohorts. The primary outcome was the 1-year incidence of immune-related adverse events (irAEs). Standard Cox models and Fine-Gray competing risk models (accounting for death) were used to estimate hazard ratios (HRs) and subdistribution hazard ratios (sHRs), respectively.</p><p><strong>Results: </strong>After matching, 22,672 patients (11,336 per group) were analyzed. In standard Cox analysis, PD-L1 inhibitors were associated with a lower risk of skin rash (HR 0.66, 95% CI 0.56-0.78), colitis (HR 0.79, 0.71-0.87), and nephritis (HR 0.71, 0.54-0.94) compared to PD-1 inhibitors. The competing risk analysis revealed that all-cause mortality was the overwhelmingly dominant outcome. Consequently, PD-L1 inhibitor use was associated with uniformly lower sHRs for every irAE analyzed (range: 0.85-0.88), with the sHR for mortality itself at 0.88 (0.84-0.92). This pattern, indicating the safety signal was heavily confounded by survival, was consistent across sex and age subgroups but more pronounced in males and older patients.</p><p><strong>Conclusion: </strong>PD-L1 inhibitors are associated with a lower risk of specific irAEs. However, mortality is the dominant competing risk in advanced cancer, fundamentally shaping safety assessments. Real-world studies must account for competing mortality to avoid distorted conclusions.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147648780","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":"Correction to: GPX4 is a key ferroptosis regulator orchestrating T cells and CAR-T-cells sensitivity to ferroptosis.","authors":"Marta Kłopotowska, Iwona Baranowska, Szymon Hajduk, Anna Jurga, Natalia Leśniowska, Michał Łaźniewski, Monika Granica, Marta Krawczyk, Milena Dziewicka, Agnieszka Graczyk, Jan Słupski, Radosław Zagożdżon, Dariusz Plewczynski, Magdalena Winiarska, Malgorzata Bajor","doi":"10.1007/s00262-025-04194-x","DOIUrl":"10.1007/s00262-025-04194-x","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13057162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629759","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}