Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Mass cytometry reveals classical monocytes, NK cells and ICOS+ CD4+ T cells associated with pembrolizumab efficacy in lung cancer patients.

Abstract

PURPOSE: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of non-small cell lung cancer (NSCLC), but predictive biomarkers of their efficacy are imperfect. The primary objective is to evaluate circulating immune predictors of pembrolizumab efficacy in advanced NSCLC patients. EXPERIMENTAL DESIGN: We use high-dimensional mass cytometry (CyTOF) in baseline blood samples of advanced NSCLC patients treated with pembrolizumab. CyTOF data are analyzed by machine-learning algorithms (Citrus, tSNE) and confirmed by manual gating followed by principal component analysis (BGA). RESULTS: We analyze 27 patients from the seminal KEYNOTE-001 study (median follow-up of 60.6 months). We demonstrate that blood baseline frequencies of classical monocytes, NK cells and ICOS+ CD4+ T cells are significantly associated with improved objective response rates, progression-free survival and overall survival (OS). Additionally, we report that a baseline immune peripheral score combining these three populations strongly predicts pembrolizumab efficacy (OS: HR=0.25 95%CI=0.12-0.51, p<0.0001). CONCLUSIONS: As this immune monitoring is easy in routine practice, we anticipate our findings may improve prediction of ICI benefit in advanced NSCLC patients.