Circulating immune-profile as predictor of outcome in advanced NSCLC patients treated with nivolumab

Abstract

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 2months. 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 CD3f, perforin and granzyme in NKCD56dimsubset. 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.