title: Tumour and host cell PD-L1 is required to mediate suppression of anti-tumour immunity in mice.
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.
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Lau
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Cheung
authors.affiliation: Department of Translational Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Lianoglou
authors.affiliation: Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haley
authors.affiliation: Department of Translational Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Klara
authors.initials: K
authors.lastname: Totpal
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanders
authors.affiliation: Department of Pathology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.affiliation: Department of Pathology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Patrick
authors.identifier: 0000-0002-3411-1257
authors.initials: P
authors.lastname: Caplazi
authors.affiliation: Department of Biomarker Development, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McBride
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Chiu
authors.affiliation: Department of Translational Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hong
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Grogan
authors.affiliation: Department of Translational Oncology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Javinal
authors.affiliation: Department of Discovery Oncology, Genentech, Inc. 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Yauch
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Irving
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Belvin
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Jeong M
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Cancer Immunology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: Maike
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D018345:Mice, Knockout; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor