Concurrent High PD-L1 Expression and CD8+ Immune Cell Infiltration Predict PD-1 Blockade Efficacy in Advanced EGFR-Mutant NSCLC Patients

Abstract

Objectives: The effectiveness of PD-1 blockade therapy in advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is limited. We investigated whether patient characteristics, PD-L1 expression, and immune cell (IC) status in the tumor microenvironment (TME) were associated with PD-1 blockade therapy outcomes.

Materials and methods: We retrospectively reviewed patients with advanced EGFR-mutant NSCLC treated with PD-1 blockade (nivolumab or pembrolizumab) between January 2016 and March 2018. The PD-L1 expression tumor proportion score (TPS) and types and distribution of ICs (CD8, PD-1, CD204, tumoral, and stromal) in the TME were analyzed.

Results: Among 57 EGFR-mutant NSCLC patients treated with PD-1 blockade, 39 patients had sufficient tissues for analyzing the TME. The overall response rate (ORR) of PD-1 blockade was 12.3%. Only tumoral CD8 positive (CD8⁺) IC status was significantly associated with the response (median tumoral CD8⁺ICs: 299/mm² vs. 115/mm², P < .01). Among the 6 patients with concurrent high PD-L1 expression (TPS: ≥ 50%)/high tumoral CD8⁺ ICs (≥ 205/mm²), 5 (83.3%) showed a response and a significantly longer progression-free survival (PFS) (PFS: 9.4M vs. 1.8M, P < .01). In contrast, none of the 7 patients with high PD-L1 expression/low tumoral CD8⁺ICs (<205/mm²) showed a response.

Conclusion: Concurrent high PD-L1 expression and high tumoral CD8⁺ ICs could predict the response and longer PFS of PD-1 blockade therapy in EGFR-mutant patients.

Keywords: CD8 positive (CD8+); Epidermal growth factor receptor (EGFR)-mutant patient; Non-small cell lung cancer (NSCLC); Programmed death-ligand 1 (PD-L1); Tumor microenvironment (TME).