The effect of neoadjuvant therapy on PD-L1 expression and CD8 lymphocyte density in non-small cell lung cancer

Abstract PD-L1 expression is the routine clinical biomarker for the selection of patients to receive immunotherapy in non-small cell lung cancer (NSCLC). However, the application and best timing of immunotherapy in the resectable setting is still under investigation. We aimed to study the effect of chemotherapy on PD-L1 expression and tumor infiltrating lymphocytes (TIL), which is to date still poorly understood. This retrospective, single-centre study cohort comprised 96 consecutive patients with NSCLC resected in 2000-2016 after neoadjuvant therapy, including paired chemo-na?ve specimens in 57 cases. A biologically matched control cohort of 114 primary resected cases was included. PD-L1 expression, CD8+ TIL density and tertiary lymphoid structures were assessed on whole slides and correlated with clinico-pathological characteristics and survival. Seven/57 and 12/57 cases had lower respectively higher PD-L1 expressions after neoadjuvant therapy. Most cases (n = 38) had no changes in PD-L1 expression and the majority of these showed PD-L1 < 1% in both samples (23/38 [60.5%]). CD8+ TILs density was significantly higher after chemotherapy (p = 0.031) in paired resections. Neoadjuvant cases showed no difference in PD-L1 expression or CD8+ TILs density compared to the chemotherapy na?ve control cohort. In univariable analyses, higher CD8+ TILs density, higher numbers of tertiary lymphoid structures but not PD-L1 expression were significantly associated with better survival. Increased PD-L1 expression after neoadjuvant chemotherapy was visually associated with worse 5-year survival, lacking statistical significance probably due to the low number of cases. PD-L1 expression is mostly unchanged after neoadjuvant chemotherapy. However, an increase of PD-L1 expression after neoadjuvant therapy could be associated with worse survival.