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 Celljournal_title
Cancer cellauthors
Johnston RJ,Comps-Agrar L,Hackney J,Yu X,Huseni M,Yang Y,Park S,Javinal V,Chiu H,Irving B,Eaton DL,Grogan JLdoi
10.1016/j.ccell.2014.10.018subject
Has Abstractpub_date
2014-12-08 00:00:00pages
923-937issue
6eissn
1535-6108issn
1878-3686pii
S1535-6108(14)00422-Xjournal_volume
26pub_type
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