Journal article
Inhibiting the unconventionals: Importance of immune checkpoint receptors in γδ T, MAIT, and nkt cells
Department of Health Technology, Technical University of Denmark1
Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark2
T-Cell Signaling and Development, Experimental & Translational Immunology, Department of Health Technology, Technical University of Denmark3
In recent years, checkpoint inhibitor (CPI) therapy has shown promising clinical responses across a broad range of cancers. However, many patients remain unresponsive and there is need for improvement. CPI therapy relies on antibody-mediated neutralization of immune inhibitory or checkpoint receptors (ICRs) that constitutively suppress leukocytes.
In this regard, the clinical outcome of CPI therapy has primarily been attributed to modulating classical MHC-restricted αβ T cell responses, yet, it will inevitably target most lymphoid (and many myeloid) populations. As such, unconventional non-MHC-restricted gamma delta (γδ) T, mucosal associated invariant T (MAIT) and natural killer T (NKT) cells express ICRs at steady-state and after activation and may thus be affected by CPI therapies.
To which extent, however, remains unclear. These unconventional T cells are polyfunctional innate-like lymphocytes that play a key role in tumor immune surveillance and have a plethora of protective and pathogenic immune responses. The robust anti-tumor potential of γδ T, MAIT, and NKT cells has been established in a variety of preclinical cancer models and in clinical reports.
In contrast, recent studies have documented a pro-tumor effect of innate-like T cell subsets that secrete pro-inflammatory cytokines. Consequently, understanding the mechanisms that regulate such T cells and their response to CPI is critical in designing effective cancer immunotherapies that favor anti-tumor immunity.
In this Review, we will discuss the current understanding regarding the role of immune checkpoint regulation in γδ T, MAIT, and NKT cells and its importance in anti-cancer immunity.
Language: | English |
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Publisher: | MDPI |
Year: | 2021 |
Pages: | 4647 |
ISSN: | 20726694 |
Types: | Journal article |
DOI: | 10.3390/cancers13184647 |
ORCIDs: | Catafal-Tardos, Elisa , Baglioni, Maria Virginia and Bekiaris, Vasileios |