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 CD8⁺CD20⁺ 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 CD8⁺CD20⁺ 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) 免疫疗法产生抗药性，但其潜在机制尚不完全清楚。我们在此报告，编码 B 细胞表面标记 CD20 的基因MS4A1在人类结肠直肠癌中显着下调。此外，结直肠癌中MS4A1的表达水平与患者生存率呈正相关。对来自公共数据库的 scRNA-Seq 数据集的分析表明，MS4A1 也在 T 细胞亚群中表达。一张CD8 ⁺ CD20 ⁺T细胞亚群存在于邻近的非肿瘤性结肠中，但在人结肠直肠癌的肿瘤中消失。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 nivolumab 结合 T 细胞表现出显着更高的 MS4A1 表达。我们的研究结果表明，CD8 ⁺ CD20 ⁺ T 亚群在宿主癌症免疫监视和肿瘤微环境中发挥作用，通过 PD-L1 依赖性机制抑制该 T 亚群。