Baseline circulating myeloid-derived suppressor cells and response to PD-1 inhibitor in non-small cell lung cancer patients.

Abstract

145 Background: Inhibitors of immune checkpoint PD-1/PD-L1 (ICI) have become a care standard in non-small cell lung cancer (NSCLC). Despite promising results, some patients cannot take advantage of immunotherapy effects. Nowadays, neither predictive nor prognostic circulating biomarkers have been found in order to select patients or to predict response to ICI. Myeloid-derived suppressor cells (MDSC) are potent immunity suppressors and may represent both a potential prognostic and a predictive biomarker. Methods: Peripheral blood samples regarding 54NSCLC patients treated with nivolumab and 5 healthy donors were prospectively included. Early-MDSC: e-MDSC (LIN-/CD14-/CD15-/HLA-DR-/CD33+), monocytic-MDSC: M-MDSC (HLA-DR low/-/CD14+/CD15-/CD11b+), polymorphonuclear-MDSC: PMN-MDSC (HLA-DR low/-/CD14-/CD15+/CD11b+) were analyzed through flow cytometry. MDSC percentage was calculated from viable peripheral blood mononuclear cells. We assessed if e-MDSC,M-MDSC and PMN-MDSC levels detected before anti-PD-1 therapy correlate with both progression-free survival (PFS) and overall survival (OS). Results: 54 patients were prospectively included: 41 with adenocarcinoma and 13 with squamous NSCLC. When compared to healthy donors, patients had significantly higher levels of circulating e-MDSC(median (range): 0.13% (0-10.9) vs0.02%(0.01-0.14), p = 0.04) and M-MDSC (median (range): 4.55% (0.08-24.18) vs1.36% (0.77-3.76), p = 0.01). Cox proportional hazard regression analysis showed that high level of M-MDSC before anti-PD-1 therapy was associated with OS (HR [CI95%]: 1.08 [1.01; 1.15],p = 0.02) and PFS (HR [CI95%]: 1.07 [1.01;1.14], p = 0.02). No prognostic impact was observed regarding e-MDSC and PMN-MDSC. Conclusions: Our study suggests that a baseline circulating high level of M-MDSC is associated with poor survival. M-MDSC may be a predictive and prognostic biomarker in NSCLC patients treated with anti-PD1. Further studies have been scheduled, including MDSC monitoring during anti-PD1 treatment, in order to confirm our findings. These data would be interesting for the development of combined therapy, targeting the suppressive environment, with ICI.