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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Johnston RJ,Comps-Agrar L,Hackney J,Yu X,Huseni M,Yang Y,Park S,Javinal V,Chiu H,Irving B,Eaton DL,Grogan JL

doi

10.1016/j.ccell.2014.10.018

subject

Has Abstract

pub_date

2014-12-08 00:00:00

pages

923-937

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(14)00422-X

journal_volume

26

pub_type

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