Cancer immunology research最新文献

{"title":"Automated Computational Flow Cytometry Correlates Decreasing Neutrophil-to-Lymphocyte Ratio to Improved Survival in NSCLC After Immune Checkpoint Blockade.","authors":"Katrien L A Quintelier, Maaike M Hofman, Mandy van Brakel, Cor H Lamers, Ron H J Mathijssen, Daphne W Dumoulin, Cor van der Leest, Ruth Seurinck, Christianne Groeneveldt, Sarah Bonte, Reno Debets, Sofie Van Gassen, Marcella Willemsen, Joachim G J V Aerts, Yvan Saeys","doi":"10.1158/2326-6066.CIR-25-0662","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-25-0662","url":null,"abstract":"<p><p>Immune checkpoint blockade (ICB) therapy is transforming non-small cell lung cancer (NSCLC) treatment and prolonging overall survival (OS). However, not all patients are responsive. Using computational cytometry analysis to identify immune cell subsets and early dynamic changes, we aimed to unravel the mechanisms underlying diverse responses to ICB in NSCLC. Peripheral blood from 34 NSCLC patients treated with nivolumab monotherapy was collected at three time points (baseline, week 2 and 4, i.e. TP1, TP2 and TP3). Six flow cytometry panels provided comprehensive immune cell profiling, and an R-pipeline was designed for data analysis. Differences in abundances, ratios, and functional marker expression were explored in relation to survival. Two additional cohorts were collected and processed similarly. The computational pipeline gave reliable results and and is generalizable to new patient cohorts. A decrease in the neutrophil-to-lymphocyte ratio (NLR) between TP2 and TP3 correlated with longer OS. Additionally, patients with an increase in CD8+ T cells between TP2 and TP3 had a higher survival probability. Lastly, we identified a CD11c+ eosinophil subset that increased in patients with a longer OS. Overall, the automated computational approach could be used to analyze clinical multicenter cytometry data in an objective and reproducible way. Moreover, potential dynamic biomarkers to assess prognosis during ICB therapy in NSCLC were identified, including changes in NLR, CD8+ T cells and CD11c+ eosinophils. This provides a foundation for further research, emphasizing validation of the pipeline and biomarkers in larger, diverse cohorts and independent datasets to assess robustness and generalizability.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBA2-High Osteosarcoma Suppresses Immune Infiltration by Autophagy-Mediated MHC-I Degradation.","authors":"Lingfeng Yu, Mengpan Li, Tongtong Liu, Jiangpeng Wu, Huanliang Meng, Wenyuan Xu, Weisong Zhao, Hao Zhu, Zhen Wang, Shibing Guo, Zhuoying Wang, Mengxiong Sun, Tao Zhang, Yafei Jiang, Jing Han, Xiaojun Ma, Wei Sun, Yingqi Hua, Zhengdong Cai","doi":"10.1158/2326-6066.CIR-25-1321","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-25-1321","url":null,"abstract":"<p><p>Osteosarcoma (OS) responds poorly to immune-checkpoint blockade (ICB), and the molecular drivers of its immune-cold state remain unclear. Using multi-omics analyses, we identified an immune-cold OS subtype characterized by enrichment of protein SUMOylation and found the SUMO E1 subunit UBA2 as a key driver. UBA2 was anomalously upregulated in OS cohorts and linked to worse outcomes. Functionally, UBA2 promoted autophagy, thereby exerting noncanonical pro-tumor and immunosuppressive effects. Mechanistically, UBA2 catalyzed SUMO2-dependent SUMOylation of SESN2, enhancing autophagic flux. At the immune interface, UBA2 did not alter the expression of immune checkpoint molecules but reduced surface MHC-I through NBR1-mediated autophagy-lysosomal degradation, thereby limiting CD8⁺ T-cell infiltration. In vivo, pharmacologic UBA2 inhibition with ML-792 slowed tumor growth and sensitized tumors to ICB therapy. Together, these findings show that UBA2 links SUMOylation to autophagy-driven loss of antigen presentation and immune exclusion, highlighting the UBA2-autophagy-MHC-I axis as a therapeutic target and potential biomarker in OS.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VSIG4 Restricts Hepatocellular Carcinoma Control by Suppressing Tumor-Specific CD8+ T-cell Immunity in the Tumor Microenvironment.","authors":"Jinglong Guo, Siddheshvar Bhela, Monica Sharma, Giulia Protti, Shiuh-Ming Luoh, Siyue Wang, Natalie S Firmino, Dragos C Dasoveanu, Caleb Chan, Veronica Ibarra-Lopez, Conrad Foo, Rajiv Jesudason, Sandra Rost, Tina Scholl, James Ziai, Laetitia Comps-Agrar, Yulei Wang, Sören Müller, Andrey S Shaw, Jing Li, Shannon J Turley, Wenxian Fu","doi":"10.1158/2326-6066.CIR-25-0836","DOIUrl":"10.1158/2326-6066.CIR-25-0836","url":null,"abstract":"<p><p>Immunotherapies have revolutionized the treatment of hepatocellular carcinoma (HCC), yet their response rates remain limited, highlighting the need for new therapeutic targets. In this study, we found that V-set and immunoglobulin domain-containing 4 (VSIG4) is predominantly expressed by macrophages in both mouse and human HCC, with high VSIG4 expression correlating with poor prognosis in patients with HCC. In autochthonous HCC models, VSIG4 deficiency in mice promoted tumor-specific CD8+ T-cell abundance, intratumoral infiltration, and effector function in the tumor microenvironment, resulting in better tumor control and significantly enhanced efficacy of anti-PD-L1 and anti-VEGF combination treatments. Furthermore, we observed that VSIG4+ macrophages colocalize with CD8+ T cells in HCC and that VSIG4 directly mediates T cell suppression in ex vivo and in vitro studies. These findings suggest that VSIG4 is a critical inhibitor of antitumor immunity in HCC and may be targeted for improved immunotherapies.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"718-732"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLK1 Promotes Myeloid-Derived Suppressor Cell Trafficking and Reprograms the Tumor Microenvironment by Activating Hippo/YAP Signaling in Colorectal Cancer.","authors":"Peisi Li, Yumo Xie, Dawang Zhou, Xuan Li, Qishan Liu, Ziming Li, Xiaoxia Liu, Jinxin Lin, Meijin Huang, Qian Yan, Yanxin Luo, Huichuan Yu, Xiaolin Wang","doi":"10.1158/2326-6066.CIR-25-0766","DOIUrl":"10.1158/2326-6066.CIR-25-0766","url":null,"abstract":"<p><p>Colorectal cancer is a highly heterogeneous malignancy characterized by complex interactions between tumor cells and the immune system. The tumor microenvironment (TME) plays a crucial role in colorectal cancer progression and response to therapy. However, the mechanisms regulating TME composition remain poorly understood because of the genetic and phenotypic diversity of tumor cells. In this study, we investigated the tumor-intrinsic factors contributing to TME formation and evaluated genotype-based combination strategies to enhance the efficacy of immunotherapy in colorectal cancer. Using RNA sequencing, single-cell analysis, and immunohistochemistry (IHC), we identified pro-oncogenic proteins associated with low immune activation. Functional studies using in vitro co-culture systems, subcutaneous colorectal tumor models, flow cytometry, and IHC revealed a role for CDC-like kinase 1 (CLK1) in tumor progression and immunosuppressive TME remodeling. Mechanistically, CLK1 activation led to hyperactivation of the Hippo signaling pathway, promoting nuclear translocation of Yes-associated protein (YAP) and subsequent transcriptional upregulation of the chemokine CXCL1. Elevated CLK1 expression correlated with increased infiltration of myeloid-derived suppressor cells (MDSC) and impaired antitumor immune responses. Knockdown (KD) of CLK1 significantly reduced MDSC recruitment and restored CD8+ T-cell activity. Moreover, combined CLK1 KD and anti-PD-1 therapy enhanced intratumoral CD8+ T-cell infiltration to a greater extent and elicited robust antitumor responses in murine colorectal cancer models. Collectively, our findings identify the CLK1-Hippo/YAP-CXCL1 signaling axis as a regulator of immune evasion and TME remodeling in colorectal cancer and highlight the potential of therapeutically targeting this axis to improve the efficacy of immune checkpoint blockade.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"875-891"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178069","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":"Intratumoral Tertiary Lymphoid Structures Characterized by a B Cell-Related Signature Elicit Antitumor Effect through HAPLN3 in Hepatocellular Carcinoma.","authors":"Qianwen Zeng, Yujun Liu, Jingying Chen, Qiaoyi Chen, Zebin Chen, Liting Peng, Zhijuan Li, Kai Lei, Xiaoxuan Lin, Shijia Liu, Ruiyan Xuan, Ruiming Liang, Zhihang Chen, Chuankai Zhang, Changyi Liao, Youmei Kang, Tianhong Su, Shuling Chen, Ming Kuang, Junbin Liao, Jianping Guo, Li Tan","doi":"10.1158/2326-6066.CIR-25-0758","DOIUrl":"10.1158/2326-6066.CIR-25-0758","url":null,"abstract":"<p><p>The existence of intratumoral tertiary lymphoid structures (TLS) has been reported to be correlated with reduced recurrence of hepatocellular carcinoma (HCC). However, the cellular characteristics and driving mechanisms of TLSs in HCC remain largely unknown. In this study, we compared the clinical outcomes of TLSs in HCC using whole-exome sequencing, bulk RNA sequencing, and single-cell RNA sequencing on a cohort of 339 patients with HCC belonging to different TLS groups. Intratumoral TLSs were significantly associated with improved recurrence-free survival in HCC (P = 0.00013), with higher maturity of TLSs correlating with better prognosis (P = 0.00033). A B cell-related seven-gene signature effectively predicted TLS presence (area under the curve = 0.78) and patient prognosis, outperforming previously reported signatures, which were validated in situ by spatial transcriptomic data. Bulk and single-cell transcriptomic analyses revealed that TLS-positive (TLS+) tumors were immunologically active and strongly associated with immunotherapy response signatures. IgG-producing plasma cells, identified as key effector subsets enriched in TLS+ tumors, exhibited clonal expansion, somatic hypermutation, and high-affinity antibody production. Among potential tumor-enriched TLS-associated genes, HAPLN3 was overexpressed in TLS+ HCC and induced high serum antibody titers (P = 0.0032). Spatial transcriptomics and in vivo experiments confirmed that HAPLN3 promotes B-cell activation, leading to suppressed tumor growth. Administration of HAPLN3 protein displayed immunostimulatory and antitumor effects in an orthotopic mouse model. These findings reveal that targeting TLS-associated B-cell responses or leveraging HAPLN3-specific immunity may offer therapeutic avenues for improving immunotherapy outcomes in HCC. See related Spotlight, p. 716.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"771-791"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Presence of CD11c+ B Cells with Potent Effector Memory Phenotype in Lung Adenocarcinoma Correlates with Overall Patient Survival.","authors":"Sharmila Sambanthamoorthy, Yan Ren, Tatiana K Galvez, Benjamin King, Scot D Liu, Brian A Kidd, Debbie A Law, Nicole Baumgarth","doi":"10.1158/2326-6066.CIR-25-0635","DOIUrl":"10.1158/2326-6066.CIR-25-0635","url":null,"abstract":"<p><p>Tumor-infiltrating B lymphocytes (TIL-B) are increasingly recognized as favorable prognostic markers in multiple cancer types, and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment naïve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors. In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, whereas CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in patients with treatment-naïve LUAD compared with normal tissue and blood. In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells, and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL12, IL21, and TNFα secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicate that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"811-826"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146177295","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":"A Sampling of Highlights from the Literature: Article Recommendations from Our Deputy and Senior Editors.","authors":"","doi":"10.1158/2326-6066.CIR-14-5-WWR","DOIUrl":"https://doi.org/10.1158/2326-6066.CIR-14-5-WWR","url":null,"abstract":"","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":"14 5","pages":"715"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL10R Inhibition Induces Neutrophil Tumoricidal Activity.","authors":"Danny N Khalil, Ricardo Gomez, Amit Regev, Fadi Samaan, Yacine Marouf, Sadna Budhu, Daniel Hirschhorn, Isabell Schulze, Jessica A Lavery, Nicholas Ceglia, Samuel S Freeman, Vivien I Maltez, Jaynia M Garcia, Nathan Suek, Chien-Huan Weng, Christopher R Cabanski, Sébastien Monette, Yevgeniy Romin, Yanyun Li, Ronan Chaligne, Michael J Yellin, Tibor Keler, Deena M Maurer, Anne-Laure Flamar, Lucia Morgado-Palacin, Levi M Mangarin, James J Harding, Wungki Park, Jaclyn P Lyman, Stephen Maddock, Mark H O'Hara, Ghassan K Abou-Alfa, Robert H Vonderheide, Eileen M O'Reilly, Ronald N Germain, Jedd D Wolchok, Taha Merghoub","doi":"10.1158/2326-6066.CIR-25-0834","DOIUrl":"10.1158/2326-6066.CIR-25-0834","url":null,"abstract":"<p><p>Although the role of neutrophils in modulating antitumor T-cell responses has been extensively studied, their direct effects on tumor cells remain less well understood. In this study, we investigated whether neutrophils have the capacity to directly kill tumor cells independently of T cells. We found that anti-CD40-based therapy, when combined with IL10 receptor blockade, initiates a Batf3-dependent pathway in which IL12 and IFNγ secretion results in oncolytic neutrophil activity. Using a combination of microscopy, single-cell, and functional assays, we observed that killing of tumor cells by neutrophils is dependent on physical contact and degranulation. This degranulation-mediated killing is associated with an atypical dynamic invasive neutrophil phenotype. In line with our preclinical findings, our phase I trial of anti-CD40 shows that circulating IL12, IFNγ, and IL10 increase in response to anti-CD40, whereas our phase Ib/2 PRINCE study shows that lower circulating IL10 is associated with favorable overall survival (OS) specifically among anti-CD40-treated patients. Finally, we found that neutrophil expansion with granulocyte colony-stimulating factor is associated with improved OS, specifically in patients treated with anti-CD40, suggesting that this pathway may be amenable to therapeutic intervention in patients with advanced cancer.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"733-750"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917082","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":"Engineered CCR7 Overexpression Enhances Nodal CAR T-cell Homing and Cytotoxicity toward B-cell Lymphoma.","authors":"Maria Zschummel, Mario Bunse, Anna-Lena Spierling, Anna Li, Jara J Joedicke, Anca Margineanu, Susanne Blachut, Eric Lars-Helge Lindberg, Jorge Ruiz-Orera, Norbert Hübner, Armin Rehm, Uta E Höpken","doi":"10.1158/2326-6066.CIR-25-1381","DOIUrl":"10.1158/2326-6066.CIR-25-1381","url":null,"abstract":"<p><p>Anti-CD19 chimeric antigen receptor (CAR) therapy demonstrated remarkable efficacy against hematologic malignancies. However, B-cell malignancies with lymph node (LN) involvement frequently remain resistant. In this study, we show that CAR T cells downregulated the chemokine receptor CCR7, crucial for nodal homing, during manufacturing. Consequently, in vitro migration toward the respective chemokines and in vivo migration to LNs was severely impaired. To improve nodal CAR T-cell trafficking, we engineered anti-CXCR5 CAR T cells, targeting mature lymphoma, with stable CCR7 expression (CAR.CCR7). CCR7 engineering of human and mouse CAR T cells restored migratory capacity and LN homing. Additionally, we observed enhanced CAR-mediated killing in CCR7-engineered anti-CXCR5 and anti-CD19 CARs alike, a process that was independent of increased cytokine secretion. Mechanistically, CCR7 overexpression was associated with an altered expression of genes involved in cytoskeletal rearrangement and faster killing kinetics. CCR7 accumulated in mature CAR synapses, supporting the costimulatory role of CCR7 within immunologic synapses. Therapeutically, improved LN recruitment and enhanced killing of CAR.CCR7 T cells improved lymphoma eradication in mice.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"827-844"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL1R2 Deficiency Unleashes Neutrophil-Mediated Antitumor Potential in Sarcoma.","authors":"Andrea Mariancini, Domenico Supino, Sarah N Mapelli, Aycan Meral, Silvia Carnevale, Irene Di Ceglie, Giovanni Pezone, Marika Ventura, Monica Dambra, Julian Swatler, Rachele Di Donato, Francesca Albano, Raffaella Bonecchi, Anna Rigatelli, Francesco Scavello, Giovanna Grieco, Federica Riva, Cem Gabay, Alberto Mantovani, Sebastien Jaillon, Elena Magrini, Cecilia Garlanda","doi":"10.1158/2326-6066.CIR-25-0651","DOIUrl":"10.1158/2326-6066.CIR-25-0651","url":null,"abstract":"<p><p>Interleukin 1 (IL1) plays dual functions in cancer. It promotes cancer-related inflammation and progression but also influences leukocyte functional activation. IL1 receptor 2 (IL1R2) functions as an IL1 decoy receptor, inhibiting IL1 activity. In this study, we investigated the contribution of IL1R2 in tuning IL1-dependent effects in mouse models of cancer, including colorectal cancer, lung cancer, and primary and metastatic transplantable and chemically induced sarcoma. Even though the prominent role of IL1 is protumoral, IL1R2 deficiency was selectively associated with reduced sarcoma growth, whereas it was irrelevant in other preclinical models investigated. IL1R2 deficiency was associated with a massive infiltration of neutrophils in the tumor, neutrophilia, and increased extramedullary emergency granulopoiesis. Neutrophils were crucial for tumor control in IL1R2-deficient mice. Immunophenotypic and transcriptional profiling of sarcoma-infiltrating neutrophils revealed that IL1R2 deficiency was associated with higher expression of activation or maturation markers and gene expression reprogramming, with downregulation of pathways associated with protumoral functions. In patients with sarcoma, the IL1R2 deficiency gene signature correlated with better clinical outcomes. Thus, this study shows that IL1R2 tunes IL1-driven cancer-associated emergency granulopoiesis and neutrophil functional activation to an antitumor mode in sarcomas and reveals the antitumor potential of neutrophils in this tumor.</p>","PeriodicalId":9474,"journal":{"name":"Cancer immunology research","volume":" ","pages":"751-770"},"PeriodicalIF":8.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13136881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455795","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}