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Nat Commun. 2017 Feb 21;8:14572. doi: 10.1038/ncomms14572.

Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice.

Author information

1
Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
2
Department of Translational Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
3
Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA.
4
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080, USA.
5
Department of Pathology, Genentech, Inc., South San Francisco, California 94080, USA.
6
Department of Biomarker Development, Genentech, Inc., South San Francisco, California 94080, USA.
7
Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, California 94080, USA.
8
Department of Discovery Oncology, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, USA.

Abstract

Expression of PD-L1, the ligand for T-cell inhibitory receptor PD-1, is one key immunosuppressive mechanism by which cancer avoids eradication by the immune system. Therapeutic use of blocking antibodies to PD-L1 or its receptor PD-1 has produced unparalleled, durable clinical responses, with highest likelihood of response seen in patients whose tumour or immune cells express PD-L1 before therapy. The significance of PD-L1 expression in each cell type has emerged as a central and controversial unknown in the clinical development of immunotherapeutics. Using genetic deletion in preclinical mouse models, here we show that PD-L1 from disparate cellular sources, including tumour cells, myeloid or other immune cells can similarly modulate the degree of cytotoxic T-cell function and activity in the tumour microenvironment. PD-L1 expression in both the host and tumour compartment contribute to immune suppression in a non-redundant fashion, suggesting that both sources could be predictive of sensitivity to therapeutic agents targeting the PD-L1/PD-1 axis.

PMID:
28220772
PMCID:
PMC5321797
DOI:
10.1038/ncomms14572
[Indexed for MEDLINE]
Free PMC Article

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