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Background Predictive biomarkers of immune checkpoint inhibitors (ICIs) efficacy in NSCLC are still an unmet goal. PD-L1 expression at tissue level (tPD-L1) is not steadily assessable in metastatic setting and, although routinely recommended, its dynamic nature hinders an accurate estimation. Thus, the aim of our study was to determine whether embodying genetic, tissue and circulating PD-L1 status may predict ICI response in NSCLC patients. To encompass PD-L1/PD-1 axis, we investigated the incidence of PD-1 receptor on circulating T-lymphocytes. Methods Peripheral blood (PB) samples from 80 consecutive ICI-treated NSCLC patients were collected at baseline. Soluble PD-L1 (sPD-L1) was measured by Human/Cynomolgus Monkey PD-L1/B7-H1 Immunoassay (R&D Systems). PD-L1 polymorphisms (rs2282055, rs4143815) were determined by RT PCR using TaqMan® method. FACS analysis was performed to detect PD-1 expression on T cells. Available tissue sections were immunohistochemically stained for tPD-L1 scoring. All these parameters were correlated with patient characteristics, survival outcome and response to treatment. Results sPD-L1 values ranged from 14.8 to 189.8 pg/ml (median 62.8 pg/ml). High sPD-L1 and low number of PB CD8+PD-1+ lymphocytes were detected in NSCLC cases displaying ECOG PS = 2, >3 metastatic sites, liver and pleural involvement (p Conclusion Our preliminary results support sPD-L1 as a promising biomarker of ICI benefit. The simultaneous assessment of the pool size of PB PD1+ effector cells might implement the strategy to predict NSCLC survival and response to treatment. Legal entity responsible for the study University Hospital of Parma. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e14514 Background: Detection of predictive markers of anti-PD-1/PD-L1 antibodies activity is of pivotal interest in non-small cell lung cancer (NSCLC). This study aimed to identify a circulating immuno-profile as predictor of outcome in NSCLC patients treated with nivolumab Methods: A peripheral blood immuno-profile evaluation was performed at baseline (T0), after 2 (T1) and 4 cycles (T2) of bi-weekly nivolumab in advanced pre-treated NSCLC patients from two Italian Institutions. First tumor assessment was performed after 4 cycles and then every 2 months. FACS analysis of lymphocyte subpopulations [CD3, CD4, CD8, NK (CD56), Treg (FOXP3) and MDSC] was performed. Absolute and % changes of lymphocyte subsets together with their functional and proliferative activity were assessed. Quali-quantitative leucocyte composition at baseline and its variation during therapy were correlated with tumor response and survival. Results: In the overall population of 54 treated patients, baseline Neutrophil-to-Lymphocyte ratio and NK count, lymphocyte count and CD4 variations during therapy showed a statistically significant prognostic role (p < 0.001; p = 0.012; p < 0.001; p = 0.010, respectively). Among 31 patients (squamous carcinoma, n = 17; adenocarcinoma, n = 14) in which all 3 time-points samples were available, 19 were responders (response and stable disease) and 12 non-responders. In responders, absolute numbers of total NK and NKCD56dim subset were higher at baseline and their increase between T0 and T1 was statistically significant (p < 0.05). Responders also displayed increased cytotoxic capability as shown by a higher baseline expression of CD3ζ, perforin and granzyme in NKCD56dim subset. No significant variation was documented in absolute number and functional activity of CD4+ and CD8+ lymphocytes. A higher percentage of CD8+PD-1+ cells at baseline was observed in responders, while non-responders showed a statistically significant increase in the absolute number of MDSC during therapy (p < 0.05). Conclusions: The number and function of NKs and the frequency of PD-1 expression in CD8+ cells could represent predictive peripheral immuno-biomarkers for nivolumab treatment in advanced NSCLC.