Inhibiting the Unconventionals: Importance of Immune Checkpoint Receptors in γδ T, MAIT, and NKT Cells.
Elisa Catafal TardosMaria Virginia BaglioniVasileios BekiarisPublished in: Cancers (2021)
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.
Keyphrases
- induced apoptosis
- immune response
- cell cycle arrest
- signaling pathway
- dna damage
- magnetic resonance imaging
- public health
- stem cells
- squamous cell carcinoma
- ejection fraction
- papillary thyroid
- toll like receptor
- chronic kidney disease
- cell therapy
- inflammatory response
- risk assessment
- human health
- childhood cancer
- patient reported outcomes
- young adults
- electronic health record
- case control
- ulcerative colitis