Dynamic changes in PD-L1 expression and CD8+ T cell infiltration in non small cell lung cancer following chemoradiation therapy

Objectives: The treatment for stage III non-small cell lung cancer (NSCLC) is quite variable because stage III NSCLC is a heterogenous disease. Programmed death ligand 1 (PD-L1) and CD8(+) tumor infiltrating lymphocytes (TILs) are thought to be related to treatment outcome in many tumors. To improve treatment outcome in stage III NSCLC, it is necessary to obtain data on PD-L1 expression and CDS+ TIL counts following CCRT and their relationship to treatment outcome. Materials and methods: We retrospectively enrolled 43 patients with stage III NSCLC treated with neoadjuvant CCRT followed by surgery at Yonsei Cancer Center Severance Hospital in Korea between June 2008 and October 2010. PD-L1 level and CD8(+) TIL numbers in tumors following CCRT were analyzed by immunohistochemistry, and their association with patient survival was evaluated with Kaplan-Meier method. Results: More than half patients (52%) showed up- or downregulation of PD-L1 expression, and most patients (81%) showed change in CD8(+) TIL counts by CCRT. Patients with PD-L1 expression following CCRT tended to have shorter recurrence free survival (RFS) (P = 0.182) or overall survival (OS) (P = 0.215) compared to the ones without PD-L1 expression. In the survival analysis with pre-CCRT specimens, neither RFS nor OS showed statistically significant differences. Patients with increased CD8(+). TIL counts following CCRT regardless of pathological response strongly showed longer OS (median: not reached vs. 14.2 months for others; P = 0.017). Conclusions: CCRT dynamically alters PD-L1 expression and CD8(+) TIL numbers in stage III NSCLC. Our data provide a rationale for combining CCRT and immunotherapy for the treatment of potentially resectable NSCLC.