对于免疫治疗，癌症患者的反应存在广泛差异，发现与积极结果相关的参数是非常感兴趣的。在这里，我们通过时间飞行高维流式细胞术（CyTOF）和Meso Scale Discovery（MSD）多细胞因子测量，对非小细胞肺癌（NSCLC）患者接受抗PD1疗法的外周血样本进行了长期监测。我们发现循环CD8+细胞和CD8+CD101hiTIM3+（CCT T）亚群的比例较高与免疫治疗的临床反应较差显著相关。一致地，在大多数反应者的整个多周期治疗方案期间，CD8+T细胞和CCT T细胞频率始终较低；从基线开始，CCT T细胞中更高的杀伤细胞凝集素样受体亚家族G成员1（KLRG1）表达与更长的无进展生存期相关。在体外刺激时，反应者的CCT T细胞产生的细胞因子水平（包括IL-1β、IL-2、IL-8、IL-22和MCP-1）明显高于非反应者。总体而言，我们的结果为了解肺癌患者对免疫检查点阻断疗法的有利反应提供了免疫学景观的长期观察。© 2023. Springer Nature Limited.

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.© 2023. Springer Nature Limited.