Treg/CD137+ T cell balance as a novel biomarker of survival in advanced non-addicted NSCLC patients treated with immunotherapy as first-line

Anti-PD1 treatment, administered alone(PDL1>50%) or combined with chemotherapy (PDL1<50%), is the standard of care in non-oncogenic addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments’ success, only 20-30% fully respond to therapies, highlighting the need to identify novel predictive and prognostic biomarkers. In several solid tumors, the active CD137+T cells and the immunosuppressive regulatory T cells (Tregs) or myeloid-derived suppressive cells (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to immunotherapy and clinical outcomes. In this study, we investigated the role of CD137+T cells, Tregs and MDSCs in NSCLC patients as possible biomarkers. Peripheral blood mononuclear cells derived from 55 NSCLC patients treated with immunotherapy as first-line, were analyzed, at baseline, for the levels of CD137+ CD137+PD1+T cell subsets, Tregs, and MDSCs by cytofluorimetry. These parameters were correlated with therapy response, Overall Survival (OS), and Progression-free survival (PFS). Circulating CD137+ and CD137+PD1+T cells (total, CD8 and CD4) positively correlated with response to therapy. Patients with high percentage of CD3+CD137+, CD3+CD137+PD1+ (total and CD8) had prolonged OS and PFS. In these patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, while high levels of Treg was correlated with favorable survival. Moreover, the balance between Treg/CD137+T cells and PMN-MDSC/CD137+T cells was higher in non-responder patients and associated with poor survival. CD137+T cells and Tregs also resulted as two positive independent prognostic factors. We proposed CD137+/CD137+PD1+T cell subsets and PMN(Lox1+)-MDSCs as predictors of the response to treatments. CD137+T cells and Treg was identified as positive prognostic factor and analyzed as Treg/CD137+T cells ratio recognized patients with longer survival.