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.
Original language | English (US) |
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Pages (from-to) | E10119-E10126 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 115 |
Issue number | 43 |
DOIs | |
State | Published - Oct 23 2018 |
Keywords
- Atezolizumab
- Cancer immunotherapy
- Checkpoints
- PD-1
- PD-L1
ASJC Scopus subject areas
- General