Arid3b suppresses CD8 + T cell infiltration and function in microsatellite-stable colorectal cancer via Runx3

作者：Shuo Wang, Sen Hou, Ce Luo, Haorui Zhang, Yiteng Jin, Rui Zhang, Yanping Zhao, Xiaoyu Xiong, Rui Guo, Chao Wang, Yudi Bao, Liang Wen, Deng Pan, Yingjiang Ye, Zexian Zeng, Zhidong Gao · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-73241-7 · 研究领域：Cancer Immunotherapy and Biomarkers、Chromatin Remodeling and Cancer、Protein Degradation and Inhibitors

Microsatellite-stable/proficient mismatch repair (MSS/pMMR) colorectal cancer (CRC) is characterized by a cold tumor microenvironment, with limited CD8⁺ T cell infiltration and poor responsiveness to immune checkpoint inhibitors (ICIs). Here, using an in vivo CRISPR/Cas9 screen in a CMT93 cell-derived murine tumor model, we identify Arid3b as a key negative regulator of CD8⁺ T cell infiltration and antitumor activity. Genetic ablation of Arid3b in CD8⁺ T cells significantly enhances their intratumoral accumulation and promotes robust tumor control. Mechanistically, Arid3b deficiency upregulates Runx3, driving a tissue-resident memory-like phenotype and effector function. Notably, the benefits conferred by Arid3b deficiency are abrogated upon Runx3 deletion, indicating a RUNX3-dependent mechanism. Together, targeting ARID3B could offer a promising strategy to reshape the tumor microenvironment and sensitize MSS CRC to immunotherapy.