{"title":"IL-27 boosts cytotoxic T cells in cancer","authors":"Alexandra Flemming","doi":"10.1038/s41577-025-01147-4","DOIUrl":null,"url":null,"abstract":"<p>Cytotoxic T lymphocytes (CTLs) in tumours are often dysfunctional. Bréart et al. investigated the association between cytokines and CTLs in human tumours and found a correlation between <i>IL27</i> expression and CTL infiltration. In syngeneic mouse models, treatment with an IL-27-encoding plasmid or half-life-enhanced IL-27, with or without anti-PD-L1, improved tumour rejection without overt toxicity. Single-cell RNA sequencing of mouse CTLs showed that IL-27 induces the expression of cytotoxicity genes, such as <i>Gzmb</i>, and downregulates genes linked to exhaustion, such as <i>Tox</i>. In patients with metastatic urothelial bladder carcinoma or non-small-cell lung cancer, high IL-27 expression was associated with improved responses to PD-L1-targeted therapy, and in vitro exhaustion assays with human CTLs showed that IL-27 promotes the differentiation of cytotoxic and effector memory T cells while suppressing dysfunction-associated markers. Overall, IL-27 seems to support CTL fitness and cytotoxicity and may be an attractive therapeutic target in cancer.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"34 1","pages":""},"PeriodicalIF":67.7000,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41577-025-01147-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cytotoxic T lymphocytes (CTLs) in tumours are often dysfunctional. Bréart et al. investigated the association between cytokines and CTLs in human tumours and found a correlation between IL27 expression and CTL infiltration. In syngeneic mouse models, treatment with an IL-27-encoding plasmid or half-life-enhanced IL-27, with or without anti-PD-L1, improved tumour rejection without overt toxicity. Single-cell RNA sequencing of mouse CTLs showed that IL-27 induces the expression of cytotoxicity genes, such as Gzmb, and downregulates genes linked to exhaustion, such as Tox. In patients with metastatic urothelial bladder carcinoma or non-small-cell lung cancer, high IL-27 expression was associated with improved responses to PD-L1-targeted therapy, and in vitro exhaustion assays with human CTLs showed that IL-27 promotes the differentiation of cytotoxic and effector memory T cells while suppressing dysfunction-associated markers. Overall, IL-27 seems to support CTL fitness and cytotoxicity and may be an attractive therapeutic target in cancer.
期刊介绍：
Nature Reviews Immunology is a journal that provides comprehensive coverage of all areas of immunology, including fundamental mechanisms and applied aspects. It has two international standard serial numbers (ISSN): 1474-1733 for print and 1474-1741 for online. In addition to review articles, the journal also features recent developments and new primary papers in the field, as well as reflections on influential people, papers, and events in the development of immunology. The subjects covered by Nature Reviews Immunology include allergy and asthma, autoimmunity, antigen processing and presentation, apoptosis and cell death, chemokines and chemokine receptors, cytokines and cytokine receptors, development and function of cells of the immune system, haematopoiesis, infection and immunity, immunotherapy, innate immunity, mucosal immunology and the microbiota, regulation of the immune response, signalling in the immune system, transplantation, tumour immunology and immunotherapy, and vaccine development.
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