Significance of immune checkpoint proteins in EGFR-mutant non-small cell lung cancer

Abstract

Objectives: To characterize the expression of PD-L1, PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC).

Materials and methods: Samples from 90 patients with newly diagnosed advanced stage NSCLC harboring EGFR mutations and treated with first line EGFR tyrosine kinase inhibitors (TKI) within 3 months of diagnosis were stained for CTLA-4, PD-L1, PD-1, TIM-3 and CD3 expression by immunohistochemistry.

Results: PD-L1 was present in at least 1% of immune and tumor cells in 44% and 59% of samples, respectively. In multivariate analysis, increased CD3 immune shaped cell (ISC) counts (HR 2.805, p=0.034) and high PD-L1 tumor H-score (HR 3.805, p=0.022) was associated with a shorter progression free survival and high CTLA-4 ISC counts was associated with borderline overall survival significance (HR 1.054, p=0.061).

Conclusion: Tumor PD-L1 expression was significantly associated with a shorter PFS whereas immune cell CTLA-4 may be prognostic for OS. Our findings support the ongoing development of CTLA-4 and PD1/PD-L1 inhibitors in this important molecularly defined subset of lung adenocarcinoma.

Keywords: Cytotoxic T-lymphocyte antigen-4; Epidermal growth factor receptor mutations; Non-small cell lung cancer; Programmed death ligand-1; T-cell immunoglobulin and mucin-domain containing-3.