CD8型
免疫系统
生物
免疫学
细胞毒性T细胞
封锁
免疫疗法
PD-L1
癌症研究
T细胞
肺癌
癌症
细胞
细胞因子
医学
受体
内科学
体外
遗传学
作者
Daniela S. Thommen,Viktor H. Koelzer,Petra Herzig,Andreas Roller,Marcel P. Trefny,Sarah Dimeloe,Anna Kiialainen,Jonathan Hanhart,Catherine Schill,Christoph Hess,Spasenija Savic Prince,Mark Wiese,Didier Lardinois,Ping‐Chih Ho,Christian Klein,Vaios Karanikas,Kirsten D. Mertz,Ton N. Schumacher,Alfred Zippelius
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-06-11
卷期号:24 (7): 994-1004
被引量:751
标识
DOI:10.1038/s41591-018-0057-z
摘要
Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1-) from non-small-cell lung cancer patients. PD-1T T cells showed a markedly different transcriptional and metabolic profile from PD-1N and PD-1- lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention.
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