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01-11-2018 | Review

TIGIT: a novel immunotherapy target moving from bench to bedside

Authors: Benjamin L. Solomon, Ignacio Garrido-Laguna

Published in: Cancer Immunology, Immunotherapy | Issue 11/2018

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.

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Title: TIGIT: a novel immunotherapy target moving from bench to bedside
Authors: Benjamin L. Solomon
Ignacio Garrido-Laguna
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 11/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2246-5

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PD-1/PD-L1 co-inhibition shapes anticancer T cell immunodominance: facing the consequences of an immunological ménage à trois

Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung

TCR repertoire profiling of tumors, adjacent normal tissues, and peripheral blood predicts survival in nasopharyngeal carcinoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer