Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39.

IF 12.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2025-04-07 Epub Date: 2025-02-05 DOI:10.1084/jem.20240445

Sang-Nee Tan, Jing Hao, Jing Ge, Yazheng Yang, Liguo Liu, Jia Huang, Meng Lin, Xiaohong Zhao, Genyu Wang, Zhiying Yang, Ling Ni, Chen Dong

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Abstract

Regulatory T (Treg) cells are known to impede antitumor immunity, yet the regulatory mechanisms and functional roles of these cells remain poorly understood. In this study, through the characterization of multiple cancer models, we identified a substantial presence of peripherally induced Treg cells in the tumor microenvironment (TME). Depletion of these cells triggered antitumor responses and provided potent therapeutic effects by increasing functional CD8+ T cells. Fate-mapping and transfer experiments revealed that IFN-γ-expressing T helper (Th) 1 cells differentiated into Treg cells in response to TGF-β signaling in tumors. Pseudotime trajectory analysis further revealed the terminal differentiation of Th1-like Treg cells from Th1 cells in the TME. Tumor-resident Treg cells highly expressed T-bet, which was essential for their functions in the TME. Additionally, CD39 was highly expressed by T-bet+ Treg cells in both mouse and human tumors, and was necessary for Treg cell-mediated suppression of CD8+ T cell responses. Our study elucidated the developmental pathway of intratumoral Treg cells and highlighted novel strategies for targeting them in cancer patients.

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肿瘤中由Th1细胞转化的调节性T细胞通过CD39抑制肿瘤免疫。

众所周知，调节性T细胞（Treg）会阻碍抗肿瘤免疫，但对这些细胞的调节机制和功能作用仍知之甚少。在这项研究中，通过对多种癌症模型的表征，我们发现肿瘤微环境（TME）中存在大量外周诱导的Treg细胞。这些细胞的耗竭触发了抗肿瘤反应，并通过增加功能性CD8+ T细胞提供了有效的治疗效果。命运定位和转移实验表明，肿瘤中表达IFN-γ-的T辅助细胞（Th） 1响应TGF-β信号分化为Treg细胞。伪时间轨迹分析进一步揭示了TME中Th1样Treg细胞与Th1细胞的终端分化。肿瘤驻留Treg细胞高度表达T-bet，这对它们在TME中的功能至关重要。此外，在小鼠和人类肿瘤中，T-bet+ Treg细胞都高度表达CD39，并且是Treg细胞介导的CD8+ T细胞反应抑制所必需的。我们的研究阐明了肿瘤内Treg细胞的发育途径，并强调了针对肿瘤患者的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.