无容量
T细胞受体
生物
CD8型
肾细胞癌
T细胞
癌症研究
肾透明细胞癌
抗原
免疫学
医学
免疫系统
免疫疗法
肿瘤科
作者
Lewis Au,Emine Hatipoglu,Marc Robert de Massy,Kevin Litchfield,Gordon Beattie,Andrew Rowan,Désirée Schnidrig,R. Houston Thompson,Fiona Byrne,Stuart Horswell,Nicos Fotiadis,Steve Hazell,David Nicol,Scott T.C. Shepherd,Annika Fendler,Robert M. Mason,Lyra Del Rosario,Kim Edmonds,Karla Lingard,Sarah Sarker
出处
期刊:Cancer Cell
[Cell Press]
日期:2021-10-28
卷期号:39 (11): 1497-1518.e11
被引量:235
标识
DOI:10.1016/j.ccell.2021.10.001
摘要
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.
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