Soluble PD-L1 and Circulating CD8+PD-1+ and NK Cells Enclose a Prognostic and Predictive Immune Effector Score in Immunotherapy Treated NSCLC patients

•Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immune effector score•Blood-based multiparametric models might non-invasively predict ICI response Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC). Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD-1+ and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (IeffS). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response. High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P