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Cancer Immunol Immunother. 2018 Nov;67(11):1659-1667. doi: 10.1007/s00262-018-2246-5. Epub 2018 Sep 19.

TIGIT: a novel immunotherapy target moving from bench to bedside.

Author information

1
Oncology Division, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Suite 2100, Salt Lake City, UT, 84112, USA. Benjamin.solomon@hci.utah.edu.
2
Oncology Division, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Suite 2100, Salt Lake City, UT, 84112, USA.
3
Center for Investigational Therapeutics, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

Abstract

Treatment strategies for patients with advanced solid tumors have traditionally been based on three different paradigms: surgery, cytotoxics (chemotherapy or radiation therapy) and targeted therapies. Immunotherapy has emerged as a novel treatment paradigm in our armamentarium. Unfortunately, most patients still do not benefit from immunotherapy. These patients often have "cold tumors" characterized by a paucity of effector T cells in the tumor microenvironment, low mutational load, low neoantigen burden and often an immunosuppressive tumor microenvironment. TIGIT is an immunoreceptor inhibitory checkpoint that has been implicated in tumor immunosurveillance. Expression of TIGIT has been demonstrated in both NK cells and T cells and plays a role in their activation and maturation. TIGIT competes with immunoactivator receptor CD226 (DNAM-1) for the same set of ligands: CD155 (PVR or poliovirus receptor) and CD112 (Nectin-2 or PVRL2). TIGIT's role in tumor immunosurveillance is analogous to the PD-1/PD-L1 axis in tumor immunosuppression. Both TIGIT and PD-1 are upregulated in a variety of different cancers. Anti-TIGIT antibodies have demonstrated synergy with anti-PD-1/PD-L1 antibodies in pre-clinical models. Currently, there are multiple first-in-man phase I trials hoping to exploit this new pathway and improve response rates with existing immunotherapies.

KEYWORDS:

Combination immunotherapy; Immuno-oncology; Immunotherapy; TIGIT

PMID:
30232519
DOI:
10.1007/s00262-018-2246-5
[Indexed for MEDLINE]

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