结直肠癌
免疫系统
癌症研究
免疫检查点
肿瘤微环境
T细胞
细胞毒性T细胞
生物
生物标志物
主要组织相容性复合体
封锁
MHC I级
免疫疗法
抗原
细胞
下调和上调
免疫逃逸
免疫学
逃避(道德)
细胞毒性
医学
转录组
大肠癌小鼠模型的建立
癌症
免疫监视
获得性免疫系统
肿瘤浸润淋巴细胞
癌症免疫疗法
免疫
先天免疫系统
作者
Chuwei Liu,Heng Liang,Peipei Wang,Min Xiao,Yuyan Zheng,Shijia Yan,Yuan Deng,Ruhua Liu,Arabella Wan,Zhi Wang,Xiongbin Lu,Wu Song,Weiling He,Guohui Wan
标识
DOI:10.1158/2326-6066.cir-25-0433
摘要
Immune checkpoint blockade (ICB) has transformed colorectal cancer therapy, yet the majority of microsatellite-stable colorectal cancers remain refractory because of insufficient tumor-immune cell cross-talk. Identifying molecular regulators that modulate the tumor immune microenvironment (TIME) is crucial for expanding ICB efficacy. In this study, we identified HNRNPA2B1, an RNA-binding protein prominently upregulated in colorectal cancer, as a key driver of immune evasion. Despite low cytotoxicity to normal cells, HNRNPA2B1 rewired the TIME by suppressing Cxcl9/Cxcl10-Cxcr3 signaling, CD8+ T-cell infiltration, and MHC class I antigen presentation, resulting in a noninflamed ("cold") tumor state. HNRNPA2B1 deletion reprogramed the TIME, enhanced CD8+ T cell-mediated tumor clearance, and sensitized microsatellite-stable colorectal cancers to ICB. A computational A2B1 score was developed to quantify HNRNPA2B1's impact on tumor-immune interactions, and it strongly correlated with immune infiltration, epithelial-mesenchymal transition status, and patient prognosis, supporting its potential role as a biomarker for ICB responsiveness in colorectal cancer.
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