肿瘤浸润双阴性调节性T细胞预测鼻咽癌T细胞免疫治疗的预后。

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-05-01 DOI:10.1016/j.xcrm.2025.102096

Xiu-Feng Liu, Bin Song, Chang-Bin Sun, Qian Zhu, Jian-Hui Yue, Yu-Jing Liang, Jia He, Xi-Liang Zeng, Ye-Chi Qin, Qiu-Yan Chen, Hai-Qiang Mai, Xi Zhang, Jiang Li

{"title":"肿瘤浸润双阴性调节性T细胞预测鼻咽癌T细胞免疫治疗的预后。","authors":"Xiu-Feng Liu, Bin Song, Chang-Bin Sun, Qian Zhu, Jian-Hui Yue, Yu-Jing Liang, Jia He, Xi-Liang Zeng, Ye-Chi Qin, Qiu-Yan Chen, Hai-Qiang Mai, Xi Zhang, Jiang Li","doi":"10.1016/j.xcrm.2025.102096","DOIUrl":null,"url":null,"abstract":"Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3+ T cell clusters within 26 TIL infusion products: 11 CD3+CD8+ TILs, 2 CD3+CD4+ TILs, and 1 CD3+CD8-CD4- double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56+ and four CD56- subsets. Among them, CD56-KZF2+ (DN) TILs are predominantly suppressive. (DN) TILs inhibit CD8+ TIL expansion via Fas-FasL, transforming growth factor β (TGF-β), and interleukin (IL)-10 signaling. Distinct CD8+ T subsets differentially impact on TIL-ACT outcomes, while 9 baseline TME gene signatures and 14 intracellular T cell genes hold prognostic value. Our findings identify predictive TIL subsets and biomarkers for TIL-ACT outcomes.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102096"},"PeriodicalIF":11.7000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147895/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.\",\"authors\":\"Xiu-Feng Liu, Bin Song, Chang-Bin Sun, Qian Zhu, Jian-Hui Yue, Yu-Jing Liang, Jia He, Xi-Liang Zeng, Ye-Chi Qin, Qiu-Yan Chen, Hai-Qiang Mai, Xi Zhang, Jiang Li\",\"doi\":\"10.1016/j.xcrm.2025.102096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3+ T cell clusters within 26 TIL infusion products: 11 CD3+CD8+ TILs, 2 CD3+CD4+ TILs, and 1 CD3+CD8-CD4- double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56+ and four CD56- subsets. Among them, CD56-KZF2+ (DN) TILs are predominantly suppressive. (DN) TILs inhibit CD8+ TIL expansion via Fas-FasL, transforming growth factor β (TGF-β), and interleukin (IL)-10 signaling. Distinct CD8+ T subsets differentially impact on TIL-ACT outcomes, while 9 baseline TME gene signatures and 14 intracellular T cell genes hold prognostic value. Our findings identify predictive TIL subsets and biomarkers for TIL-ACT outcomes.\",\"PeriodicalId\":9822,\"journal\":{\"name\":\"Cell Reports Medicine\",\"volume\":\" \",\"pages\":\"102096\"},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2025-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147895/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Reports Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xcrm.2025.102096\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2025.102096","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

采用肿瘤浸润淋巴细胞（til）的过继细胞疗法（ACT）在实体瘤治疗中取得了临床成功。我们分析了来自同步放化疗加TIL- act （NCT02421640）随机2期临床研究的47种TIL输注产品和62种预处理肿瘤微环境（TMEs）。利用单细胞和大体积RNA测序以及流式细胞术，我们在26种TIL输注产品中鉴定了14个CD3+ T细胞簇：11个CD3+CD8+ TIL， 2个CD3+CD4+ TIL和1个CD3+CD8-CD4-双阴性（DN） TIL。（DN） TILs与不良的TIL-ACT结果显著相关，表现出活化的调节性T细胞样表型，包括两个CD56+和四个CD56-亚群。其中CD56-KZF2+ (DN) TILs主要是抑制性的。（DN） TILs通过Fas-FasL、转化生长因子β (TGF-β)和白细胞介素(IL)-10信号传导抑制CD8+ TIL的扩增。不同的CD8+ T亚群对TIL-ACT结果的影响不同，而9个基线TME基因特征和14个细胞内T细胞基因具有预后价值。我们的研究结果确定了TIL- act结果的预测性TIL亚群和生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3⁺ T cell clusters within 26 TIL infusion products: 11 CD3⁺CD8⁺ TILs, 2 CD3⁺CD4⁺ TILs, and 1 CD3⁺CD8^-CD4^- double-negative (DN) TIL. (DN) TILs, significantly associated with poor TIL-ACT outcomes, exhibit an activated regulatory T cell-like phenotype and include two CD56⁺ and four CD56^- subsets. Among them, CD56^-KZF2⁺ (DN) TILs are predominantly suppressive. (DN) TILs inhibit CD8⁺ TIL expansion via Fas-FasL, transforming growth factor β (TGF-β), and interleukin (IL)-10 signaling. Distinct CD8⁺ T subsets differentially impact on TIL-ACT outcomes, while 9 baseline TME gene signatures and 14 intracellular T cell genes hold prognostic value. Our findings identify predictive TIL subsets and biomarkers for TIL-ACT outcomes.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.