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Novel human immunomodulatory T cell receptors and their double-edged potential in autoimmunity, cardiovascular disease and cancer

Cellular & Molecular Immunology volume 18, pages 919–935 (2021)Cite this article

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Abstract

In the last decade, approaches based on T cells and their immunomodulatory receptors have emerged as a solid improvement in treatments for various types of cancer. However, the roles of these molecules in the therapeutic context of autoimmune and cardiovascular diseases are still relatively unexplored. Here, we review the best known and most commonly used immunomodulatory T cell receptors in clinical practice (PD-1 and CTLA-4), along with the rest of the receptors with known functions in animal models, which have great potential as modulators in human pathologies in the medium term. Among these other receptors is the receptor CD69, which has recently been described to be expressed in mouse and human T cells in autoimmune and cardiovascular diseases and cancer. However, inhibition of these receptors individually or in combination by drugs or monoclonal antibodies generates a loss of immunological tolerance and can trigger multiple autoimmune disorders in different organs and immune-related adverse effects. In the coming decades, knowledge on the functions of different immunomodulatory receptors will be pivotal for the development of new and better therapies with less harmful side effects. In this review, we discuss the roles of these receptors in the control of immunity from a perspective focused on therapeutic potential in not only cancer but also autoimmune diseases, such as systemic lupus erythematosus, autoimmune diabetes and rheumatoid arthritis, and cardiovascular diseases, such as atherosclerosis, acute myocardial infarction, and myocarditis.

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Acknowledgements

This study was supported by competitive grants from the Ministerio de Ciencia, Innovación y Universidades, through the Carlos III Institute of Health-Fondo de Investigación Sanitaria (PI19/00545) to P.M.; CIBER Cardiovascular (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and cofunding by Fondo Europeo de Desarrollo Regional FEDER) to P.M.; and CAM (S2017/BMD-3671-INFLAMUNE-CM) from the Comunidad de Madrid to P.M. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). R.B.-D. is supported by the Formación de Profesorado Universitario (FPU16/02780) program of the Spanish Ministry of Education, Culture and Sports.

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Authors and Affiliations

  1. Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

    Pilar Martín, Rafael Blanco-Domínguez & Raquel Sánchez-Díaz

  2. CIBERCV, Madrid, Spain

    Pilar Martín & Raquel Sánchez-Díaz

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  1. Pilar Martín
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  2. Rafael Blanco-Domínguez
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  3. Raquel Sánchez-Díaz
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Correspondence to Pilar Martín.

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Martín, P., Blanco-Domínguez, R. & Sánchez-Díaz, R. Novel human immunomodulatory T cell receptors and their double-edged potential in autoimmunity, cardiovascular disease and cancer. Cell Mol Immunol 18, 919–935 (2021). https://doi.org/10.1038/s41423-020-00586-4

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