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

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

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. 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 CD101hiTIM3 cells determine the response.

CYTOTOXIC T cells; T cells; KILLER cell receptors; NON-small-cell lung carcinoma; PROGRAMMED cell death 1 receptors; PROGRESSION-free survival; IMMUNE checkpoint proteins

Nature Communications, 2023, Vol 14, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-023-40631-0