Abstract 3132: Single nucleotide polymorphisms (SNPs) in PD-L1 as predictive biomarkers for checkpoint inhibitor based-immunotherapy in caucasian patients with advanced NSCLC

Effective predictive biomarkers are needed for checkpoint inhibitors (ICI) based-immunotherapy in non-small-cell lung cancer (NSCLC). This study aims to evaluate whether single nucleotide polymorphisms (SNPs) in programmed cell death-ligand 1 (PD-L1) might effectively predict tumor response to ICI in Caucasian patients with advanced NSCLC. Peripheral blood samples and clinico-pathological data were prospectively collected from advanced NSCLC patients treated with anti-Programmed cell death protein 1 (PD-1) inhibitor nivolumab. rs822336, rs2282055 and rs4143815 PD-L1 SNPs were analysed based on previous reports available in the literature. PD-L1 SNPs were analysed following DNA extraction from stored peripheral blood lymphocytes by Taqman Real-Time PCR assay. Presence of PD-L1 SNPs were correlated with clinico-pathological data. Mechanisms underlying the effect of PD-L1 SNPs on PD-L1 expression were analysed in vitro utilizing five NSCLC cell lines, RNA expression and flow cytometry analysis as well as PROMO bioinformatic tool. PD-L1 SNPs localization were analysed utilizing Ensembl genome browser. Differences were considered statistically significant with p value< 0.05. Twenty-eight patients were included in the study. rs2282055 was present as wild type (wt) TT (rs2282055>T), GT and GG genotype in 56.25%, 34.38% and 9.38%, respectively, of patients. On the other hand, rs822336 was present as wt GG (rs822336>G), GC and CC genotype in 28.13%, 37.50% and 34.38%, respectively, of patients. Progression free survival (PFS) was significantly correlated with presence of both PD-L1 SNPs rs2282055 and rs822336 but not with rs4143815. Patients carrying GG either for rs2282055 or rs822336 had a significantly (p=0.0434 and p=0.0131, respectively) shorter PFS as compared to those carrying other PD-L1 SNP genotypes. NSCLC cell lines carrying either GG for rs2282055 or rs822336 significantly (p