Novel circulating biomarkers in HNSCC patients receiving anti-PD1 therapy: the predictive and prognostic role of immunosuppressive CD137+Treg cells and Lox-1+PMN-MDSCs

BACKGROUND-AIM Recurrent/metastatic Head and neck squamous cell carcinoma ((R/M) HNSCC) represents one of the most aggressive and immunosuppressive cancer diseases. Despite the introduction of immunotherapy with Immune checkpoint inhibitors (ICIs), only a limited number of patients obtained long-term benefits. Anti-tumor immune response is in fact defective in these patients, conferring resistance to therapies and promoting tumor progression. Therefore, the identification of novel predictive and prognostic biomarkers giving superior clinical outcomes is still an unmet clinical need in (R/M) HNSCC patients. The impact of circulating immunosuppressive cells on immunotherapy response remains unclear. In this study, we evaluated the role of regulatory T cells (total Treg, resting, active, non-suppressive, and CD137+Treg) and myeloid-derived suppressor cells (MDSCs; LOX-1+PMN-MDSC and M-MDSCs) as possible biomarkers in the blood of (R/M) HNSCC patients underwent immunotherapy. METHODS Data from 40 (R/M) HNSCC patients receiving pembrolizumab as first line treatment were prospectively reviewed. PBMCs were isolated at baseline and the levels of Tregs, LOX-1+PMN-MDSC and M-MDSC were analyzed by cytofluorimetry. The percentage of Treg and MDSC cells were correlated with clinical response rate after six months of therapy, progression-free survival (PFS), overall survival (OS) and performance status (PS). RESULTS Results showed that responder patients have significantly low levels of circulating LOX-1+PMN-MDSC (p=0.021). Moreover, patients with lower levels of LOX-1+PMN-MDSC (≤0.33%) and CD137+Treg cells (≤0.081%) have prolonged survival (p=0.03 and p=0.01 respectively). CD137+Treg cells resulted also positively correlated with PS: patients with PS=0 have lower levels of this population than patients with PS>0 (p=0.01). Multivariate analysis showed LOX-1+PMNMDSC cells (>0.33%) as independent prognostic factors correlated with PFS (p=0.01) and OS (p=0.02). CONCLUSIONS Our results indicate that the levels of circulating CD137+Treg and LOX-1+PMN-MDSC cells could predict the success of anti-cancer immunotherapy and could be used as biomarkers for prognosis, monitoring and management of (R/M) HNSCC, improving patient selection and suggesting the development of novel personalized therapeutic strategies