美国纪念斯隆-凯特琳癌症中心Alexander Y. Rudensky团队开发出不同调节性T细胞亚群在结直肠癌中的对抗性功能。该项研究成果发表在2025年12月15日出版的《免疫学》上。

课题组人员检查了CRC中肿瘤Treg细胞的异质性，并确定了两个不同的肿瘤Treg亚群，它们具有不同的Il10表达。表达白细胞介素-10 （IL-10?）的选择性耗竭Treg细胞通过解除效应CD4⁺ T细胞对IL-17产生的抑制促进肿瘤生长，从而直接刺激肿瘤细胞增殖；IL-10?的消耗Treg细胞导致肿瘤明显消退。在人类结直肠癌中，IL-10? IL-10-Treg丰度分别与预后良好和不良相关。因此，IL-10? IL-10-Treg细胞在邻近的正常结肠组织和肿瘤中表现出相反的富集模式。在不同的人类屏障组织肿瘤中观察到转录相似的Treg亚群。Treg亚群之间的这种功能二分法可以选择性地靶向肿瘤前亚群，同时在结直肠癌和其他屏障组织癌症中保留其抗肿瘤对应物。

据悉，实体器官癌中调节性T （Treg）细胞的富集通常与不良预后相关；然而，结直肠癌（CRC）是一个明显的例外。

附：英文原文

Title: Opposing functions of distinct regulatory T cell subsets in colorectal cancer

Author: Xiao Huang, Dan Feng, Sneha Mitra, Emma S. Andretta, Nima B. Hooshdaran, Aazam P. Ghelani, Eric Y. Wang, Joe N. Frost, Victoria R. Lawless, Aparna Vancheswaran, Qingwen Jiang, Cheryl Mai, Karuna Ganesh, Christina S. Leslie, Alexander Y. Rudensky

Issue&Volume: 2025-12-15

Abstract: Enrichment of regulatory T (Treg) cells in solid organ cancers is generally associated with poor prognosis; however, colorectal cancer (CRC) stands out as a notable exception. Here, we examined the heterogeneity of tumoral Treg cells in CRC and identified two distinct tumoral Treg subsets with differential Il10 expression. Selective depletion of interleukin-10-expressing (IL-10?) Treg cells promoted tumor growth by lifting the restraint on IL-17 production from effector CD4+ T cells, thereby directly stimulating tumor cell proliferation; depletion of IL-10− Treg cells led to pronounced tumor regression. In human CRC, IL-10? and IL-10− Treg abundance correlated with favorable and unfavorable prognosis, respectively. Accordingly, IL-10? and IL-10− Treg cells exhibited opposite enrichment patterns in adjacent normal colon tissues and tumors. Transcriptionally similar Treg subsets were observed across different human barrier tissue tumors. This functional dichotomy between Treg subsets may enable selective targeting of the pro-tumoral subset while preserving its anti-tumoral counterpart in CRC and other barrier tissue cancers.

DOI: 10.1016/j.immuni.2025.11.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00516-3