Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients

Abstract

Background/aim: Programmed death-ligand 1 (PD-L1) expression on tumor cells is a predictive biomarker of programmed cell death 1 (PD-1) blockade therapy. This study sought to clarify predictors of the efficacy of nivolumab in non-small cell lung cancer (NSCLC) patients with PD-L1 expression-negative tumors.

Patients and methods: We retrospectively reviewed the records of advanced NSCLC patients between January 2016 and April 2019, and investigated the predictive marker of nivolumab including the status of CD8⁺ tumor infiltrating lymphocytes (TILs).

Results: A total of 70 NSCLC patients were included. Overall response rate (ORR) and progression-free survival (PFS) were better in patients with a heavy smoking history (smoking index: SI≥600) than in those without (SI<600) [ORR: 20.6% vs. 2.8%, (p=0.02), and PFS: 2.4 months vs. 1.8 months, (p=0.04)]. A high density of CD8⁺ TILs was significantly associated with a heavy smoking history (p=0.04). Conlusion: Heavy smoking history (SI≥600), which was correlated with a large number of CD8⁺ TILs, could be a predictor of the efficacy of nivolumab in NSCLC patients with PD-L1 expression-negative tumors.

Keywords: CD8+ tumor infiltrating lymphocytes (TILs); Non-small cell lung cancer (NSCLC); nivolumab; programmed death-ligand 1 (PD-L1); smoking index.