生物
T细胞受体
CD8型
肺癌
癌症研究
细胞分化
医学
肿瘤浸润淋巴细胞
免疫系统
T细胞
抗原
免疫学
病理
基因
遗传学
作者
Paul Gueguen,Christina Metoikidou,Thomas Dupic,Myriam Lawand,Christel Goudot,Sylvain Baulande,Sonia Lameiras,Olivier Lantz,Nicolas Girard,Agathe Seguin‐Givelet,Marine Lefèvre,Thierry Mora,Aleksandra M. Walczak,Joshua J. Waterfall,Sebastián Amigorena
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-01-08
卷期号:6 (55)
被引量:77
标识
DOI:10.1126/sciimmunol.abd5778
摘要
Tumor-infiltrating lymphocytes (TILs), in general, and especially CD8+ TILs, represent a favorable prognostic factor in non-small cell lung cancer (NSCLC). The tissue origin, regenerative capacities, and differentiation pathways of TIL subpopulations remain poorly understood. Using a combination of single-cell RNA and T cell receptor (TCR) sequencing, we investigate the functional organization of TIL populations in primary NSCLC. We identify two CD8+ TIL subpopulations expressing memory-like gene modules: one is also present in blood (circulating precursors) and the other one in juxtatumor tissue (tissue-resident precursors). In tumors, these two precursor populations converge through a unique transitional state into terminally differentiated cells, often referred to as dysfunctional or exhausted. Differentiation is associated with TCR expansion, and transition from precursor to late-differentiated states correlates with intratumor T cell cycling. These results provide a coherent working model for TIL origin, ontogeny, and functional organization in primary NSCLC.
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