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The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8(+) T Cell Effector Function

The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8(+) T Cell Effector Function

Robert J Johnston, Laetitia Comps-Agrar, Jason Hackney, Xin Yu, Mahrukh Huseni, Yagai Yang, Summer Park, Vincent Javinal, Henry Chiu, Bryan Irving, Dan L Eaton, Jane L Grogan

Cancer Cell. 2014 Dec 8;26(6):923-937.

PMID: 25465800

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413152	CD226 human			Price

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