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TIGIT: a novel immunotherapy target moving from bench to bedside

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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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Abbreviations

FGL2:

Fibrinogen-like protein 2

ITT:

Immunoreceptor tail tyrosine

MTD:

Maximum-tolerated dosing

PVR:

Poliovirus receptor

PVRL2:

Poliovirus receptor-related 2

TIGIT:

T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain

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Acknowledgements

Jonathan Martinez provided the original illustration for this manuscript.

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Authors and Affiliations

  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 L. Solomon & Ignacio Garrido-Laguna

  2. Center for Investigational Therapeutics, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA

    Ignacio Garrido-Laguna

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  1. Benjamin L. Solomon
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  2. Ignacio Garrido-Laguna
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BLS was primary author of the manuscript. IG-L aided with additional content and editing.

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Correspondence to Benjamin L. Solomon.

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Solomon, B.L., Garrido-Laguna, I. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother 67, 1659–1667 (2018). https://doi.org/10.1007/s00262-018-2246-5

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  • DOI: https://doi.org/10.1007/s00262-018-2246-5

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