Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1) Journal Article


Authors: Kowanetz, M.; Zou, W.; Gettinger, S. N.; Koeppen, H.; Kockx, M.; Schmid, P.; Kadel, E. E. 3rd; Wistuba, I.; Chaft, J.; Rizvi, N. A.; Spigel, D. R.; Spira, A.; Hirsch, F. R.; Cohen, V.; Smith, D.; Boyd, Z.; Miley, N.; Flynn, S.; Leveque, V.; Shames, D. S.; Ballinger, M.; Mocci, S.; Shankar, G.; Funke, R.; Hampton, G.; Sandler, A.; Amler, L.; Mellman, I.; Chen, D. S.; Hegde, P. S.
Article Title: Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1)
Abstract: Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with nonsmall cell lung cancer (NSCLC) most likely to respond to singleagent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4, 549 cases of NSCLC. PDL1 expression on IC was more prevalent and likely reflected IFN-?-induced adaptive regulation accompanied by increased tumorinfiltrating lymphocytes and effector T cells. High PD-L1 expression on TC, however, reflected an epigenetic dysregulation of the PDL1 gene and was associated with a distinct histology described by poor immune infiltration, sclerotic/desmoplastic stroma, and mesenchymal molecular features. Importantly, durable clinical responses to atezolizumab (anti-PD-L1) were observed in patients with tumors expressing high PD-L1 levels on either TC alone [40% objective response rate (ORR)] or IC alone (22%ORR). Thus, PD-L1 expression on TC or IC can independently attenuate anticancer immunity and emphasizes the functional importance of IC in regulating the antitumor T cell response. © 2018 National Academy of Sciences. All rights reserved.
Keywords: cancer immunotherapy; pd-1; checkpoints; pd-l1; atezolizumab
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 115
Issue: 43
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2018-10-23
Start Page: E10119
End Page: E10126
Language: English
DOI: 10.1073/pnas.1802166115
PUBMED: 30297397
PROVIDER: scopus
PMCID: PMC6205493
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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  1. Jamie Erin Chaft
    289 Chaft