Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy

• Published in: Nature communications 2023-08, Vol.14 (1), p.5115-5115, Article 5115
• Main Authors: Leung, Elaine Lai-Han, Li, Run-Ze, Fan, Xing-Xing, Wang, Lily Yan, Wang, Yan, Jiang, Zebo, Huang, Jumin, Pan, Hu-Dan, Fan, Yue, Xu, Hongmei, Wang, Feng, Rui, Haopeng, Wong, Piu, Sumatoh, Hermi, Fehlings, Michael, Nardin, Alessandra, Gavine, Paul, Zhou, Longen, Cao, Yabing, Liu, Liang
• Format: Article
• Language: English
• Subjects: 13/21; 49/1; 49/47; 59/78; 631/250/1933; 631/67/1612/1350; 692/308/409; 692/699/67/1059/2325; CD8 antigen; Cytokines; Cytometry; Cytotoxicity; Dimensional analysis; Humanities and Social Sciences; Immune checkpoint inhibitors; Immunology; Immunotherapy; Interleukin 2; Interleukin 22; Interleukin 8; KLRG1 protein; Lung cancer; Lymphocytes; Lymphocytes T; Mathematical analysis; Monocyte chemoattractant protein 1; multidisciplinary; Non-small cell lung carcinoma; Parameter identification; Patients; PD-1 protein; Peripheral blood; Science; Science (multidisciplinary); Small cell lung carcinoma; Survival; Therapy
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40631-0

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 + CD101 hi TIM3 + (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. Immune checkpoint blockade therapy improved the survival rates of non-small cell lung cancer but only a proportion of patients benefit. Here authors follow the humoral and cellular immunological parameters of patients undergoing anti-PD1 therapy longitudinally and find that levels and functional properties of cytotoxic T cells, and especially CD8 + CD101 hi TIM3 + cells determine the response.