MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Abstract

Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo. Of note, MAIT cell hyperactivation during certain infections may impede their ability to elicit inflammatory and/or cytotoxic responses to secondary stimuli. In addition, MAIT cells isolated from within and from the margin of tumor masses exhibit diminished functions. We propose that MAIT cell-mediated cytotoxicity can be induced, bolstered, or restored to assist in clearing infections and potentially in reducing tumor loads. In this review, we discuss our current understanding of MAIT cells' lytic functions and highlight the pressing questions that need to be addressed in future investigations. We also offer a picture, however hypothetical at this point, of how harnessing the full cytotoxic potentials of MAIT cells may be a valuable approach in the immunotherapy of infectious and malignant diseases.

MAIT cells as attractive vaccine targets

“…MAIT cells are cytotoxic and can respond to some superantigens in the absence of ligand binding . It has been proposed that MAIT cell‐mediated cytotoxicity can be induced, augmented, or reestablished to play a protective role in microbial infections . We analyze this potential in more detail below.…”

Leveraging Public Single-Cell and Bulk Transcriptomic Datasets to Delineate MAIT Cell Roles and Phenotypic Characteristics in Human Malignancies

“…Each of these cytokines can potentially influence cancer progression or antitumor defense mechanisms (46,47). Lastly, upon encounter with MR1 + target cells, MAIT cells degranulate to release perforin and granzymes (48,49). MAIT cell-mediated oncolysis has yet to be demonstrated in vivo.…”

MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight

“…According to their restriction to the non‐classical major histocompatibility complex class I‐related (MR1) molecule , MAIT cells can only recognize a limited number of antigens, mainly metabolites of the bacterial riboflavin and folate pathway . Upon activation, they produce proinflammatory cytokines such as tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ and cytotoxic molecules such as perforin and granzyme B . Due to the high abundance of MAIT cells in the liver, we speculated that BAs may have a modulatory function on the bacterial activation of these cells.…”