小柯机器人

近日，美国德克萨斯大学Rolf A. Brekken、Huocong Huang等研究人员合作发现，间皮细胞来源的抗原呈递型癌症相关成纤维细胞诱导胰腺癌中调节性T细胞的扩增。2022年5月5日，《癌细胞》杂志在线发表了这项成果。

据研究人员介绍，最近的研究发现了一个独特的癌症相关成纤维细胞（CAF）群体，称为抗原呈递CAF（apCAF），其特点是表达主要组织相容性复合体II类分子，表明其在调节肿瘤免疫方面的功能。

通过整合多个单细胞RNA测序研究并进行强大的系谱追踪检测，研究人员发现apCAF来自于间皮细胞。在胰腺癌的进展过程中，间皮细胞通过下调间皮细胞特征和获得成纤维细胞特征形成apCAF，这一过程由白细胞介素-1和转化生长因子β诱导。apCAF以抗原特异性方式直接连接和诱导新生CD4⁺T细胞成为调节性T细胞（Treg）。此外，用一种针对间皮细胞标记物间皮素的抗体处理，可以有效地抑制间皮细胞向apCAF的转化和apCAF诱导的Treg形成。

总之，这项研究阐明了间皮细胞如何有助于胰腺癌的免疫规避，并为加强癌症免疫治疗的策略提供了启示。

附：英文原文

Title: Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer

Author: Huocong Huang, Zhaoning Wang, Yuqing Zhang, Rachana N. Pradhan, Debolina Ganguly, Raghav Chandra, Gilbert Murimwa, Steven Wright, Xiaowu Gu, Ravikanth Maddipati, Sren Müller, Shannon J. Turley, Rolf A. Brekken

Issue&Volume: 2022-05-05

Abstract: Recent studies have identified a unique cancer-associated fibroblast (CAF) population termed antigen-presenting CAFs (apCAFs), characterized by the expression of major histocompatibility complex class II molecules, suggesting a function in regulating tumor immunity. Here, by integrating multiple single-cell RNA-sequencing studies and performing robust lineage-tracing assays, we find that apCAFs are derived from mesothelial cells. During pancreatic cancer progression, mesothelial cells form apCAFs by downregulating mesothelial features and gaining fibroblastic features, a process induced by interleukin-1 and transforming growth factor β. apCAFs directly ligate and induce naive CD4+ T cells into regulatory T cells (Tregs) in an antigen-specific manner. Moreover, treatment with an antibody targeting the mesothelial cell marker mesothelin can effectively inhibit mesothelial cell to apCAF transition and Treg formation induced by apCAFs. Taken together, our study elucidates how mesothelial cells may contribute to immune evasion in pancreatic cancer and provides insight on strategies to enhance cancer immune therapy.

DOI: 10.1016/j.ccell.2022.04.011

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00173-8

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx