生物
淋巴
免疫疗法
质量细胞仪
癌症免疫疗法
CD8型
肿瘤微环境
细胞毒性T细胞
癌症研究
T细胞
癌症
免疫学
病理
免疫系统
遗传学
医学
表型
体外
基因
生物化学
作者
Maha K. Rahim,Trine Line Hauge Okholm,Kyle B. Jones,Elizabeth McCarthy,Candace C. Liu,Jacqueline L. Yee,Stanley Tamaki,Diana M. Marquez,Iliana Tenvooren,Katherine C. Wai,Alexander Cheung,Brittany Davidson,Vrinda Johri,Bushra Samad,William O’Gorman,Matthew F. Krummel,Annemieke van Zante,Alexis J. Combes,Michael Angelo,Lawrence Fong,Alain P. Algazi,Patrick K. Ha,Matthew H. Spitzer
出处
期刊:Cell
[Elsevier]
日期:2023-03-01
卷期号:186 (6): 1127-1143.e18
被引量:116
标识
DOI:10.1016/j.cell.2023.02.021
摘要
Summary
CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.
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