Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC.
Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC.
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DOI：
10.3389/fimmu.2022.1004345
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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食管鳞癌是一种高致死率、预后差的恶性肿瘤。患者免疫微环境（TME）的转录组特征对免疫抑制剂疗效的影响仍知之甚少。我们从PD-1单克隆抗体敏感和耐药患者的外周血中提取并分离免疫细胞，并进行深度单细胞RNA测序，以描述食管癌患者外周血中浸润免疫细胞的组成、谱系和功能状态的基线景观。全面分析了免疫细胞的转录组特征，解释了细胞百分比的动态变化、细胞亚型的异质性以及细胞间的相互作用。基于T细胞抗原受体的共表达和谱系追踪揭示了显著比例的高度迁移的组织间效应T细胞。GO和KEGG富集途径分析CD 8+效应T细胞ESCC_S组和ESCC_D1，2组，发现在上调的富集途径中，ESCC_S组富集了更多的肿瘤中表达的PD-L1和PD-1检查点途径（JUN/NFKBIA/FOS/KRAS/IFNG），它们也存在于T细胞受体信号通路中。MT 2A、MT 1X和MT 1 E在PD-1单克隆抗体耐药的ESCC患者中差异表达，可能与PD-1 mMAB耐药有关。本研究深入了解了食管癌患者外周免疫细胞浸润对单克隆抗体PD-1敏感性的影响，有助于促进食管癌患者的免疫治疗。
Esophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood. Here we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer. The transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB. This study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.