近日，美国Dana-Farber癌症研究所Kai W. Wucherpfennig及其小组的最新研究探明了CARM1表观遗传酶抑制肿瘤免疫中的交叉呈递树突状细胞功能。这一研究成果发表在2026年7月9日出版的国际学术期刊《科学》上。

该课题组人员发现表观遗传酶CARM1（共激活子相关精氨酸甲基转移酶1）是cDC1s而非cDC2s递呈癌症抗原的选择性负调节因子。Carm1基因的失活促进了cDC1抗原在肿瘤中的交叉呈递、激活和积累，Carm1抑制剂通过癌症新抗原疫苗增强了cDC1介导的T细胞启动。CARM1抑制增加了对cDC1功能和激活至关重要的BATF3-Jun和RelA位点的染色质可及性。转化生长因子-β调节Carm1的表达，这表明Carm1失活增强了肿瘤内cDC1功能，但不改变cDC1的稳态。这些研究发现CARM1是增强小鼠和人cDC1s抗肿瘤功能的潜在治疗靶点。

据介绍，癌症免疫周期需要交叉呈递I型常规树突状细胞（cDC1s）来诱导T细胞介导的免疫，但目前增强肿瘤内cDC1功能的治疗策略还不充分。

附：英文原文

Title: The CARM1 epigenetic enzyme inhibits cross-presenting dendritic cell function in cancer immunity

Author: Xixi Zhang, Sherin Xirenayi, Ye Zhao, Wen Wang, Yuyang Han, Miguel Sobral, Shawn Kang, Chi Zhang, Graham L. Barlow, Jason Pyrdol, Jae-Won Cho, Kun Huang, Xiaohan Ning, Martin Hemberg, Guo-Cheng Yuan, Eliezer M. Van Allen, David J. Mooney, Kai W. Wucherpfennig

Issue&Volume: 2026-07-09

Abstract: The cancer-immunity cycle requires cross-presenting type I conventional dendritic cells (cDC1s) that induce T cell–mediated immunity, but therapeutic strategies for enhancing intratumoral cDC1 function are currently inadequate. We found the epigenetic enzyme CARM1 (coactivator-associated arginine methyltransferase 1) to be a selective negative regulator of cancer antigen presentation by cDC1s but not cDC2s. Inactivation of the Carm1 gene promoted cDC1 antigen cross-presentation, activation, and accumulation in tumors, and a CARM1 inhibitor enhanced cDC1-mediated priming of T cells by means of a cancer neoantigen vaccine. CARM1 inhibition increased chromatin accessibility at BATF3-Jun and RelA sites that are critical for cDC1 function and activation. Transforming growth factor–β regulated Carm1 expression, which suggests that CARM1 inactivation enhanced intratumoral cDC1 function without altering cDC1 homeostasis. These studies identify CARM1 as a potential therapeutic target for enhancing the antitumor function of mouse and human cDC1s.

DOI: aea1200

Source: https://www.science.org/doi/10.1126/science.aea1200

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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