Abstract 5518: Tumor infiltrating B cells and tertiary lymphoid structures are associated with tumor response to PD-L1 blockade in NSCLC

Abstract

Abstract Inhibitors of the programmed cell death-1/programmed cell death ligand1 (PD-1/PD-L1) signaling axis have demonstrated sustained efficacy in NSCLC, however there are gaps in our understanding of the mechanisms of how PD-1/ PD-L1 blockade improve patient outcomes, especially as they relate to long term survival. Differential gene expression analysis in tumors from NSCLC patients who derived >12 months OS benefit on atezolizumab monotherapy showed high expression of B cell transcripts in the randomized phase II POPLAR and phase III OAK studies (> median, HR: 0.61, 95% CI 0.47-0.78, and HR=0.54, CI 0.42-0.7, p<0.001 respectively). Immunofluorescence imaging confirmed the presence of CD79+ B cells in these tumors. High expression of CD79A was associated with the presence of tertiary lymphoid structures (TLS) that in turn were associated with atezolizumab survival benefit. B cell receptor sequencing of patient biopsies pre and post atezolizumab treatment suggest clonal expansion of tumor infiltrating plasma cells in patients responsive to atezolizumab. Collectively, these results suggest that NSCLC tumor patients enriched for CD79A+ B cells and IgG+ plasma cells derive greater overall survival benefit from atezolizumab and emphasize the potential of these genes as actionable biomarkers in NSCLC. Citation Format: Namrata S. Patil. Tumor infiltrating B cells and tertiary lymphoid structures are associated with tumor response to PD-L1 blockade in NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5518.