Regulatory (FoxP3+) T cells and TGF-β predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer
Jiae Koh, Joon Young Hur, Kyoung Young Lee, Mi Soon Kim, Jae Yeong Heo, Bo Mi Ku, Jong‐Mu Sun, Se‐Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung‐Ju Ahn
Abstract
Abstract Antitumor immune responses induced by immune checkpoint inhibitors anti-PD-1 or anti-PD-L1 have been used as therapeutic strategies in advanced non-small cell lung cancer (NSCLC) patients over the last decade. Favorable antitumor activity to immune checkpoint inhibitors is correlated with high PD-L1 expression, increased tumor-infiltrating lymphocytes, and decreased suppressive immune cells including Treg cells, myeloid-derived suppressor cells, or tumor-associated macrophages in various cancer types. In this study, we investigated the potential correlation between clinical outcomes and peripheral blood immune cell profiles, specifically focused on FoxP3 + Treg cells, collected at baseline and one week after anti-PD-1 therapy in two independent cohorts of patients with NSCLC: a discovery cohort of 83 patients and a validation cohort of 49 patients. High frequencies of circulating Treg cells one week after anti-PD-1 therapy were correlated with a high response rate, longer progression-free survival, and overall survival. Furthermore, high levels of TGF-β and Treg cells were associated with favorable clinical outcomes. Our results suggest that higher levels of FoxP3 + Treg cells and TGF-β can predict a favorable response to anti-PD-1 immunotherapy in patients with advanced NSCLC.