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scRNA+ TCR-seq 揭示 NSCLC 肿瘤微环境中双 TCR T 细胞的抗肿瘤应答

英文原题:scRNA+ TCR-seq revealed dual TCR T cells antitumor response in the TME of NSCLC.

PubMed 2024/09/04(内容时间) J Immunother Cancer Q1 · IF 11.7(JCR 2025)

研究概要

TCR(T 细胞受体)复杂的起源、亚群和特征,以及肿瘤微环境(TME)中肿瘤浸润 T 淋巴细胞抗肿瘤反应背后的机制,仍不明确。

中文摘要

肿瘤浸润T淋巴细胞在肿瘤微环境(TME)中的抗肿瘤反应机制,以及T细胞受体(TCR)的复杂起源、亚群特征和相关机制仍未完全阐明。近期单细胞RNA与TCR联合测序(scRNA+TCR-seq)推动了TME分析,可深入揭示单个肿瘤浸润T细胞的起源、细胞亚群、TCR CDR3组成,以及应答/耗竭因子的表达模式。研究者分析共享的scRNA+TCR-seq数据集,发现双TCR T细胞大量存在,其特点为克隆扩增,并在非小细胞肺癌患者的血液、正常组织、癌旁组织和肿瘤组织等多种组织中具有显著迁移能力。值得注意的是,双TCR CD8阳性T细胞主要属于CXCL13阳性亚群,具有强抗肿瘤活性,并倾向驻留于肿瘤组织。相反,双TCR CD4阳性T细胞主要归为CD5阳性或LMNA阳性亚群,在不同组织类型中的分布更为均匀。利用scRNA+TCR-seq及其他前沿技术,可进一步深入研究双TCR T细胞调节抗肿瘤反应或耐受的作用和机制。这种创新方法有望为研究TME中的TIL(肿瘤浸润淋巴细胞)提供新视角和新方向。

展开英文摘要原文

The intricate origins, subsets, and characteristics of TCR (T Cell Receptor) s, along with the mechanisms underpinning the antitumor response of tumor-infiltrating T lymphocytes within the tumor microenvironment (TME) remain enigmatic. Recently, the advent of single-cell RNA+TCR-sequencing (scRNA+TCR seq) has revolutionized TME analysis, providing unprecedented insight into the origins, cell subsets, TCR CDR3 compositions, and the expression patterns of response/depletion factors within individual tumor-infiltrating T lymphocytes. Our analysis of the shared scRNA+TCR seq dataset revealed a substantial presence of dual TCR T cells, characterized by clonal hyperplasia and remarkable migratory prowess across various tissues, including blood, normal, peritumoral, and tumor tissues in non-small cell lung cancer patients. Notably, dual TCR CD8+T cells predominantly fell within the CXCL13+subset, displaying potent antitumor activity and a strong preference for tumor tissue residency. Conversely, dual TCR CD4+T cells were predominantly classified as CD5+ or LMNA+subsets, exhibiting a more even distribution across diverse tissue types. By harnessing scRNA+TCR seq and other cutting-edge technologies, we can delve deeper into the effects and mechanisms that regulate the antitumor response or tolerance of dual TCR T cells. This innovative approach holds immense promise in offering fresh perspectives and avenues for advancing research on TIL (Tumor infiltrating lymphocyte)s within the TME.

论文信息

作者
Peng Q、Xu Y、Yao X
第一作者单位
Department of Immunology, Zunyi Medical University, Zunyi, China.China
通讯作者单位
Department of Immunology, Zunyi Medical University, Zunyi, China immunology@126.com.China
期刊
Journal for immunotherapy of cancer2024 Sep 4
原文标识
PubMed 39237261 · DOI 10.1136/jitc-2024-009376