title: The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.
abstract: Tumors constitute highly suppressive microenvironments in which infiltrating T cells are "exhausted" by inhibitory receptors such as PD-1. Here we identify TIGIT as a coinhibitory receptor that critically limits antitumor and other CD8(+) T cell-dependent chronic immune responses. TIGIT is highly expressed on human and murine tumor-infiltrating T cells, and, in models of both cancer and chronic viral infection, antibody coblockade of TIGIT and PD-L1 synergistically and specifically enhanced CD8(+) T cell effector function, resulting in significant tumor and viral clearance, respectively. This effect was abrogated by blockade of TIGIT's complementary costimulatory receptor, CD226, whose dimerization is disrupted upon direct interaction with TIGIT in cis. These results define a key role for TIGIT in inhibiting chronic CD8(+) T cell-dependent responses.
authors.affiliation: Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Johnston
authors.affiliation: Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Comps-Agrar
authors.affiliation: Department of Bioinformatics and Computational Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Hackney
authors.affiliation: Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oncology Biomarker Development, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Mahrukh
authors.initials: M
authors.lastname: Huseni
authors.affiliation: Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Yagai
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Translational Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Summer
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Javinal
authors.affiliation: Department of Biochemical and Cellular Pharmacology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Chiu
authors.affiliation: Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Irving
authors.affiliation: Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Eaton
authors.affiliation: Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: grogan.jane@gene.com.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Grogan
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D055503:Protein Multimerization; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D011971:Receptors, Immunologic