MS4A1 在结直肠癌肿瘤微环境中的 T 细胞中的表达和功能。
MS4A1 expression and function in T cells in the colorectal cancer tumor microenvironment.
机构信息
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA.
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Medical College of Georgia, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
出版信息
Cell Immunol. 2021 Feb;360:104260. doi: 10.1016/j.cellimm.2020.104260. Epub 2020 Dec 14.
The majority of human colorectal cancer remains resistant to immune checkpoint inhibitor (ICI) immunotherapy, but the underlying mechanism is incompletely understood. We report here that MS4A1, the gene encoding B cell surface marker CD20, is significantly downregulated in human colorectal carcinoma. Furthermore, MS4A1 expression level in colorectal carcinoma is positively correlated with patient survival. Analysis of scRNA-Seq dataset from public database revealed that MS4A1 is also expressed in subsets of T cells. A CD8CD20 subset of T cells exists in the neighboring non-neoplastic colon but disappears in tumor in human colorectal carcinoma. Furthermore, analysis of a published nivolumab treatment dataset indicated that nivolumab-bound T cells from human patients during anti-PD-1 immunotherapy exhibit significantly higher MS4A1 expression. Our findings indicate that CD8CD20 T subset functions in host cancer immunosurveillance and tumor microenvironment suppresses this T subset through a PD-L1-dependent mechanism.
大多数人类结直肠癌仍然对免疫检查点抑制剂（ICI）免疫疗法具有抗性，但潜在机制尚不完全清楚。我们在这里报告，编码 B 细胞表面标记物 CD20 的基因 MS4A1 在人结直肠癌中显著下调。此外，结直肠癌中 MS4A1 的表达水平与患者的生存呈正相关。对公共数据库中的 scRNA-Seq 数据集的分析表明，MS4A1 也在 T 细胞亚群中表达。人类结直肠癌中存在 CD8CD20 T 细胞亚群，但在肿瘤中消失。此外，对已发表的 nivolumab 治疗数据集的分析表明，在抗 PD-1 免疫治疗期间，来自人类患者的与 nivolumab 结合的 T 细胞表现出明显更高的 MS4A1 表达。我们的研究结果表明，CD8CD20 T 细胞亚群在宿主的癌症免疫监视中发挥作用，肿瘤微环境通过 PD-L1 依赖的机制抑制这种 T 细胞亚群。
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