Patil and Nabet et al. examined the transcriptomes of 891 NSCLC patient tumors sampled prior to anti-PD-L1 or docetaxel chemotherapy. B cell-associated genes correlated with longer OS in immunotherapy-treated patients than T cell-associated genes, and three B cell signatures were identified with scRNAseq across NSCLC tumors: follicular B cells, germinal center B cells, and plasma cells. High plasma cell signatures (validated through immunofluorescence and bulk RNAseq) correlated most strongly with patient OS, as did the presence of intratumoral tertiary lymphoid structures, but only in patients later treated with anti-PD-L1 (not chemotherapy).
Contributed by Alex Najibi
ABSTRACT: Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit. Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we find a significant B cell association with extended OS with PD-L1 blockade, independent of CD8(+) T cell signals. We then derive gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA sequencing (RNA-seq) data. Importantly, we find increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B and plasma cells are also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to the efficacy of PD-L1 blockade in NSCLC.
Author Info: (1) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. Electronic address: patil.namrata@gene.com. (2) Oncology Biomarker Development, Genentech, Inc.,
Author Info: (1) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. Electronic address: patil.namrata@gene.com. (2) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. Electronic address: nabet.barzin@gene.com. (3) Oncology Bioinformatics, Genentech, Inc., South San Francisco, CA, USA. (4) Research Pathology, Genentech, Inc., South San Francisco, CA, USA. (5) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (6) Research Pathology, Genentech, Inc., South San Francisco, CA, USA. (7) OMNI Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (8) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (9) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (10) OMNI Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (11) Cancer Immunology Research, Genentech, Inc., South San Francisco, CA, USA. (12) Cancer Immunology Research, Genentech, Inc., South San Francisco, CA, USA. (13) Cancer Immunology Research, Genentech, Inc., South San Francisco, CA, USA. (14) Research Pathology, Genentech, Inc., South San Francisco, CA, USA. (15) Research Pathology, Genentech, Inc., South San Francisco, CA, USA. (16) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (17) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (18) OMNI Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (19) Clinical Science, Genentech, Inc., South San Francisco, CA, USA. (20) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (21) Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
