Impact of cytotoxic chemotherapy on PD-L1 expression in patients with non–small cell lung cancer negative for EGFR mutation and ALK fusion

Abstract

ObjectivesImmune-checkpoint inhibitors (ICIs) are now an established therapeutic option for advanced non–small cell lung cancer (NSCLC). It has remained unclear, however, whether cytotoxic chemotherapy affects the immune microenvironment in NSCLC wild type for EGFR and ALK. Materials and methodsWe retrospectively evaluated changes in programmed cell death 1–ligand 1 (PD-L1) expression, tumor mutation burden (TMB), and CD8+ tumor-infiltrating lymphocyte (TIL) density in NSCLC patients who underwent rebiopsy at the site of recurrence after postoperative platinum-based adjuvant chemotherapy, or in those who underwent rebiopsy after one or more chemotherapeutic regimens at the advanced stage. The PD-L1 tumor proportion score (TPS) and CD8+ TIL density were determined by immunohistochemistry. TMB was estimated by next-generation sequencing with a cancer gene panel (409 genes). ResultsSeventeen patients with NSCLC wild type for EGFR and ALK were enrolled. Although PD-L1 TPS tended to be increased in rebiopsy samples compared with initial biopsy tissue, this difference was not significant (P = 0.113). Seven patients showed an increase in PD-L1 TPS, with this change being pronounced in four. Two cases in which PD-L1 TPS increased from 0 to 90% or from 0 to 95% after cytotoxic chemotherapy also showed a durable response to subsequent treatment with an ICI. No substantial correlation between PD-L1 TPS and TMB was apparent either before (R = 0.112) or after (R = 0.101) chemotherapy. A moderate correlation was detected between PD-L1 TPS and CD8+ TIL density before chemotherapy (R = 0.517) and a negligible correlation after (R = 0.0219). ConclusionCytotoxic chemotherapy may change the biological characteristics of tumors including PD-L1 expression level and TMB.