T cell invigoration is associated with the clinical response to anti-PD-1 based immunotherapy in non-small cell lung cancer

Abstract Purpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1 based immunotherapy in NSCLC is unknown. Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognosis was followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Kaplan-Meier analysis was performed to draw survival curves and Cox regression analysis to confirm the independent prognostic factors of NSCLC patients. Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P<0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging were associated with better progression-free survival (PFS) and overall survival (OS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and OS (P<0.05). Conclusion: Activation of circulating Tex cells before therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.