Clinical significance of programmed death ligand-1 expression in non-small cell lung cancer (NSCLC).

Abstract

11075 Background: Programmed cell death ligand-1 (PDL1) is expressed on various human cancers and is a major mechanism for immune evasion. Preliminary evidence suggests that PDL1 expression on cancer cells predicts response to anti-PD-1 therapy. Here we report our findings using automated quantitative immunofluorescence (QIF) to determine the frequency and prognostic value of PDL1 in two independent NSCLC cohorts. Methods: Five antibodies against PDL1 were screened for sensitivity and specificity using PDL1 transfected cells, normal human placenta and tonsil. Only one monoclonal antibody (clone 5H1) met criteria for specificity. This antibody was used to assess two cohorts of NSCLC cases in TMAs. The cohorts represented 204 cases from Yale University and 340 cases from hospitals in Greece. PDL1 protein was measured using QIF analysis using AQUA method. In addition, in-situ PDL1 mRNA levels were measured in the Greek cohort using the RNAscope paired-primer assay with AQUA method. Results: PDL1 protein expression was detected in 25% and 36% of the studied cohorts, respectively. PDL1 positivity was significantly associated with the presence of tumor-infiltrating lymphocytes (TIL) in both series. Patients with PDL1 protein positivity had better outcome in both series (Log Rank: p=0.036 for Yale cohort, p=0.027 for Greek cohort). Multivariate analysis showed that PDL1 expression was associated with better outcome independent of histology, presence of TILs, and stage in the Greek cohort and marginally significant in the Yale cohort. These findings were further validated by the PDL1 in-situ mRNA measurement in the Greek cohort. PDL1 protein and mRNA levels showed a positive non-linear relationship (R2=0.14, P<0.001). Positive PDL1 mRNA was found in 53% of patients with NSCLC and was also associated with the presence of TILs and longer overall survival (31 vs. 43 months, p=0.017). Conclusions: Tumor PDL1 protein positivity is detected in 25-30% of NSCLCs and associates with increased TILs and better outcome. Elevated PDL1 mRNA occurs in a higher proportion of NSCLC cases and provides comparable prognostic information. Measurement of in situ PDL1 protein and mRNA could be of more clinical value than either method alone.