免疫系统
CD8型
免疫疗法
免疫学
T细胞
细胞毒性T细胞
免疫检查点
医学
生物
肿瘤科
癌症研究
体外
生物化学
作者
Elaine Lai‐Han Leung,Runze Li,Xing‐Xing Fan,Lily Yan Wang,Qianqian Wang,Ze‐Bo Jiang,Jumin Huang,Hudan Pan,Yue Fan,Hongmei Xu,Feng Wang,Haopeng Rui,Piu Wong,Hermi Sumatoh,Michael G. Fehlings,Alessandra Nardin,Paul R. Gavine,Lihua Zhou,Yabing Cao,Liang Liu
标识
DOI:10.1038/s41467-023-40631-0
摘要
Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.
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