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Cancer Cell. 2014 Dec 8;26(6):923-937. doi: 10.1016/j.ccell.2014.10.018. Epub 2014 Nov 26.

The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function.

Author information

1
Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
2
Department of Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
3
Department of Bioinformatics and Computational Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
4
Department of Oncology Biomarker Development, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
5
Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
6
Department of Translational Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
7
Department of Biochemical and Cellular Pharmacology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
8
Department of Cancer Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: grogan.jane@gene.com.

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.

PMID:
25465800
DOI:
10.1016/j.ccell.2014.10.018
[Indexed for MEDLINE]
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