Research Topic

MAIT Cells in Cancer and How to Target them

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About this Research Topic

Mucosal associated invariant T (MAIT) cells are an abundant human T cell population. They are cytotoxic T cells with ready innate-like type 1 and type 17 effector functions; activated in a T cell receptor (TCR)-dependent and TCR-independent manner and first responders to numerous pathogens. Although phenotypically distinct, MAIT cells are primarily characterized by a semi-invariant T cell receptor (TCR) restricted by the highly conserved MHC-1 related molecule, MR1, which binds to metabolites of folic acid, bacterially derived precursors of riboflavin and drug and drug-like molecules with variable effects on MAIT cell function.

MAIT cells infiltrate a number of tumors raising questions about their role, mechanisms of MAIT cell activation and effector function within the tumor microenvironment. Although MR1-binding tumor antigens have not been defined, numerous pathways could lead to MAIT cell activation including encounter with microbial-derived MRI-presented antigen and also TCR independent activation by cytokines. Studies suggest cancer-infiltrating MAIT cells are skewed towards tumor-promoting type-17 function. What drives this functional skewing is not understood but may explain why the degree of MAIT cell infiltration within certain tumors is associated with reduced patient survival and disease progression.

Despite their negative association with cancer progression and tumor-promoting function within some tumors, this hasn’t been a universal observation. Data suggests they have anti-tumor effects in vitro and MAIT cells are promising therapeutic candidates in cancer immunotherapy. Adoptive MAIT cell therapy or MAIT cell-targeting therapy to re-program their anti-tumor function are important avenues to be explored. Conventional T cell-based immunotherapy for the treatment of malignancy has been hindered by a number of factors including polymorphic human leukocyte antigen genotypes limiting the utility of ‘off the shelf’ T cell or chimeric antigen receptor (CAR) T cell therapy in genetically diverse human populations. Unconventional T cells such as MAIT cells, restricted by monomorphic MR1, may overcome this issue. Mechanisms of MAIT cell anti-tumor immunity warrants further exploration – such as through potent IFNγ production, TCR- and NKG2D-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity via CD16 expression. Furthermore, high expression of the ATP-binding cassette-multi-drug efflux protein 1 (MDR1) allows MAIT cells to efflux and be resistant to the effects of cytotoxic MDR1 substrates – which requires investigation and exploitation in the setting of cancer therapy.

In this research topic we welcome, Mini-Reviews and Original Research articles that discuss current knowledge of MAIT cells in cancer, explore the relationship of MAIT cells within tumor tissue to cancer progression, define MAIT cell function within the tumor microenvironment and delineate mechanisms of MAIT cell anti-tumor immunity. We also encourage discussion and studies which focus on MAIT cell-based or targeting immunotherapy. We welcome submissions under the following subtopics:

1. Current understanding of the role of MAIT cells in cancer
2. Clinical correlative studies of the relationship of MAIT cells within tumors to cancer progression
3. Interplay of MAIT cells within the tumor environment and its effects on MAIT cells function, recruitment, and survival
4. Mechanisms of MAIT cells anti-tumor immunity
5. Towards translation - MAIT cells in the cancer clinic


Keywords: Mucosal associated invariant T (MAIT) cells, anti-tumour immunity, immunotherapy, MR1, cancer


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Mucosal associated invariant T (MAIT) cells are an abundant human T cell population. They are cytotoxic T cells with ready innate-like type 1 and type 17 effector functions; activated in a T cell receptor (TCR)-dependent and TCR-independent manner and first responders to numerous pathogens. Although phenotypically distinct, MAIT cells are primarily characterized by a semi-invariant T cell receptor (TCR) restricted by the highly conserved MHC-1 related molecule, MR1, which binds to metabolites of folic acid, bacterially derived precursors of riboflavin and drug and drug-like molecules with variable effects on MAIT cell function.

MAIT cells infiltrate a number of tumors raising questions about their role, mechanisms of MAIT cell activation and effector function within the tumor microenvironment. Although MR1-binding tumor antigens have not been defined, numerous pathways could lead to MAIT cell activation including encounter with microbial-derived MRI-presented antigen and also TCR independent activation by cytokines. Studies suggest cancer-infiltrating MAIT cells are skewed towards tumor-promoting type-17 function. What drives this functional skewing is not understood but may explain why the degree of MAIT cell infiltration within certain tumors is associated with reduced patient survival and disease progression.

Despite their negative association with cancer progression and tumor-promoting function within some tumors, this hasn’t been a universal observation. Data suggests they have anti-tumor effects in vitro and MAIT cells are promising therapeutic candidates in cancer immunotherapy. Adoptive MAIT cell therapy or MAIT cell-targeting therapy to re-program their anti-tumor function are important avenues to be explored. Conventional T cell-based immunotherapy for the treatment of malignancy has been hindered by a number of factors including polymorphic human leukocyte antigen genotypes limiting the utility of ‘off the shelf’ T cell or chimeric antigen receptor (CAR) T cell therapy in genetically diverse human populations. Unconventional T cells such as MAIT cells, restricted by monomorphic MR1, may overcome this issue. Mechanisms of MAIT cell anti-tumor immunity warrants further exploration – such as through potent IFNγ production, TCR- and NKG2D-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity via CD16 expression. Furthermore, high expression of the ATP-binding cassette-multi-drug efflux protein 1 (MDR1) allows MAIT cells to efflux and be resistant to the effects of cytotoxic MDR1 substrates – which requires investigation and exploitation in the setting of cancer therapy.

In this research topic we welcome, Mini-Reviews and Original Research articles that discuss current knowledge of MAIT cells in cancer, explore the relationship of MAIT cells within tumor tissue to cancer progression, define MAIT cell function within the tumor microenvironment and delineate mechanisms of MAIT cell anti-tumor immunity. We also encourage discussion and studies which focus on MAIT cell-based or targeting immunotherapy. We welcome submissions under the following subtopics:

1. Current understanding of the role of MAIT cells in cancer
2. Clinical correlative studies of the relationship of MAIT cells within tumors to cancer progression
3. Interplay of MAIT cells within the tumor environment and its effects on MAIT cells function, recruitment, and survival
4. Mechanisms of MAIT cells anti-tumor immunity
5. Towards translation - MAIT cells in the cancer clinic


Keywords: Mucosal associated invariant T (MAIT) cells, anti-tumour immunity, immunotherapy, MR1, cancer


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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