CD8型
祖细胞
细胞毒性T细胞
生物
免疫系统
免疫检查点
T细胞
癌症研究
抗原
免疫学
免疫疗法
细胞生物学
干细胞
遗传学
体外
作者
Giorgio Gaglia,M. Burger,Cecily C. Ritch,Danae Rammos,Yang Dai,Grace E. Crossland,Sara Tavana,Simon Warchol,Alex M. Jaeger,Santiago Naranjo,Shannon Coy,Ajit J. Nirmal,Robert F. Krueger,Jia-Ren Lin,Hanspeter Pfister,Peter K. Sorger,Tyler Jacks,Sandro Santagata
出处
期刊:Cancer Cell
[Elsevier]
日期:2023-05-01
卷期号:41 (5): 871-886.e10
被引量:17
标识
DOI:10.1016/j.ccell.2023.03.015
摘要
Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes ("lymphonets") emerged as a distinctive feature of the anti-cancer immune response. Lymphonets nucleated from small T cell clusters and incorporated B cells with increasing size. CXCR3-mediated trafficking modulated lymphonet size and number, but T cell antigen expression directed intratumoral localization. Lymphonets preferentially harbored TCF1+ PD-1+ progenitor CD8+ T cells involved in responses to immune checkpoint blockade (ICB) therapy. Upon treatment of mice with ICB or an antigen-targeted vaccine, lymphonets retained progenitor and gained cytotoxic CD8+ T cell populations, likely via progenitor differentiation. These data show that lymphonets create a spatial environment supportive of CD8+ T cell anti-tumor responses.
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