文章目录

肺癌中的T细胞分化是由肿瘤突变形成的

原文发布日期：2020-05-22

英文摘要：

摘要翻译：

原文链接：

文章：

肺癌中的T细胞分化是由肿瘤突变形成的

The T cell differentiation landscape is shaped by tumour mutations in lung cancer

原文发布日期：2020-05-22

英文摘要：

Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours and whether this affects patient outcomes is unknown. Here, we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets with strong phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states was associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC.

摘要翻译：

肿瘤突变负担（Tumour mutational burden, TMB）在非小细胞肺癌（non-small cell lung cancer, NSCLC）中可以预测免疫治疗的效果，这与其免疫系统对肿瘤新抗原的识别是一致的。然而，持续暴露于抗原对于T细胞功能是有害的。目前尚不清楚TMB如何影响未经治疗肿瘤中CD4和CD8 T细胞分化，以及这种现象是否会影响患者的预后。在这里，我们通过来自接受手术切除、未经治疗NSCLC患者的高维流式分析、染色体外测（exome）、单细胞和群体RNA测序等多组学方法，探讨了这些关系。TMB与跨区域T细胞分化的偏移现象相关联，表现为TCF7表达的祖系CD4 T细胞丢失，并且增加了异常CD8和CD4 T细胞亚群的丰度，这些亚群在表型和转录特征上强烈地类似于对肿瘤抗原反应的CD8 T细胞。与这些状态重排相关的基因签名与肺癌和其他癌症患者中生存率差的结果相关联。单细胞级别的表征为NSCLC潜在的治疗策略提供了见解。