Longitudinal high-dimensional analysis identifies biomarkers of response to anti-PD-1 immunotherapy

Abstract The response to immunotherapy could be better predicted by using a wide set of biomarkers, including serum tumor markers; however, robust immune markers associated with efficacy have yet to be validated. In this study, changes in immune cell subsets from NSCLC patients treated with anti-PD1 therapy were longitudinally monitored by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines kits. The frequencies of circulating CD8+ and CD8+CD101hiTIM3+ (CCT T) subsets were significantly correlated with clinical response and survival. Enrichment of these populations in peripheral blood mononuclear cells (PBMCs) indicated a poor clinical response to ICB therapy. Cell function assays revealed that these subsets were remarkably impaired, which supported the poor outcomes observed. Additionally, longitudinal analysis showed that KLRG1 expression and cytokines were associated with the response to therapy. Overall, our results provide novel potential biomarkers for guiding the management of NSCLC patients eligible to anti-PD-1 therapy, and contribute insights for new therapeutic strategies.