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The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation

Cellular & Molecular Immunology volume 15, pages 438–446 (2018)Cite this article

Abstract

Among various immunoregulatory molecules, the B7 family of immune-checkpoint receptors consists of highly valuable targets for cancer immunotherapy. Antibodies targeting two B7 family co-inhibitory receptors, CTLA-4 and PD-1, have elicited long-term clinical outcomes in previously refractory cancer types and are considered a breakthrough in cancer therapy. Despite the success, the relatively low response rate (20–30%) warrants efforts to identify and overcome additional immune-suppressive pathways. Among the expanding list of T cell inhibitory regulators, V domain immunoglobulin suppressor of T cell activation (VISTA) is a unique B7 family checkpoint that regulates a broad spectrum of immune responses. Here, we summarize recent advances that highlight the structure, expression, and multi-faceted immunomodulatory mechanisms of VISTA in the context of autoimmunity, inflammation, and anti-tumor immunity.

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Acknowledgements

This work is supported by research funding from NCI R01 CA164225 (LW), Advancing A Healthier Wisconsin Research and Education Program (AHW REP) fund (LW), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Cancer Research Program under Award No. W81XWH-14-1-0587 (LW), Cancer Research Institute CLIP Grant (LW), pilot grant 504057 from the Melanoma Research Alliance (LW), Worldwide Cancer Research grant 16-1161 (LW and SM), NIH R01 AI102893 (SM), NCI R01 CA179363 (SM), the Nicholas Family Foundation (SM), and the Gardetto Family endowment (SM).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Milwaukee, WI 53226, USA

    Wenwen Xu, TạMinh Hiếu, Subramaniam Malarkannan & Li Wang

  2. Department of Medicine, Milwaukee, WI 53226, USA

    Subramaniam Malarkannan

  3. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA

    Subramaniam Malarkannan

  4. Blood Research Institute, 53226, Milwaukee, WI, USA

    Subramaniam Malarkannan

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Correspondence to Li Wang.

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Xu, W., Hiếu, T., Malarkannan, S. et al. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 15, 438–446 (2018). https://doi.org/10.1038/cmi.2017.148

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