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Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?

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Abstract

Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression. On the other hand, they can express a potent arsenal of cytotoxic effector molecules, NKG2D and IFN-γ, all of which have established roles in cancer immune surveillance. In this review, we highlight MAIT cells’ characteristics as they might pertain to cancer initiation, progression, or control. We discuss recent findings, including our own, that link MAIT cells to cancer, with a focus on colorectal carcinoma, as well as some of the outstanding questions in this active area of research. Finally, we provide a hypothetical picture in which MAIT cells constitute attractive targets in cancer immunotherapy.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

Apc :

Adenomatous polyposis coli

Bcl-2:

B-cell lymphoma 2

CCL:

C-C chemokine [ligand]

CCR:

C-C chemokine receptor

CEA:

Carcinoembryonic antigen

CRC:

Colorectal carcinoma

CRLM:

Colorectal liver metastasis

CXCL:

C-X-C chemokine [ligand]

CXCR:

C-X-C chemokine receptor

ERK:

Extracellular signal-regulated kinase

FOLFOX:

Leucovorin Calcium (Folinic Acid)/5-Fluorouracil/Oxaliplatin

GZM:

Granzyme

IBD:

Inflammatory bowel disease

IL-17RA:

IL-17 receptor A

iNKT:

Invariant natural killer T [cell]

IP-10:

IFN-γ-inducible protein of 10 kDa

iTCRα:

Invariant TCR α [chain]

iVα19 tg:

Invariant Vα19 TCR transgenic [mice]

JNK:

c-Jun N-terminal kinase

LAG-3:

Lymphocyte-activation gene 3

MAIT:

Mucosa-associated invariant T [cell]

MDR1:

Multi-drug resistance protein 1

MIC:

MHC class I polypeptide-related sequence

MIG:

Monokine induced by gamma interferon

MMP:

Matrix metalloproteinase

MR1:

MHC-related protein 1

NKG2D:

Natural-killer group 2, member D

PGE2 :

Prostaglandin E2

RORC:

RAR related orphan receptor C

SEB:

Staphylococcal enterotoxin B

TH1:

T helper 1

TH17:

T helper 17

TIM-3:

T cell immunoglobulin and mucin-3

TME(s):

Tumor microenvironment(s)

TRAJ:

T cell receptor alpha joining

TRAV:

T cell receptor alpha variable

ULBP/RAET:

UL16-binding protein/retinoic acid early transcript

VEGF:

Vascular endothelial growth factor

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Acknowledgements

We thank Joshua Choi and Courtney Meilleur from the Haeryfar Laboratory for participating in helpful discussions on the theme of this review.

Funding

The authors’ cited research on the subject was partially funded by a Canadian Institutes of Health Research (CIHR) operating grant (MOP-130465) to S.M. Mansour Haeryfar. Christopher R. Shaler is a CIHR postdoctoral fellowship recipient.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Western University, 1151 Richmond Street, London, ON, N6A 5C1, Canada

    S. M. Mansour Haeryfar, Christopher R. Shaler & Patrick T. Rudak

  2. Centre for Human Immunology, Western University, London, ON, Canada

    S. M. Mansour Haeryfar

  3. Lawson Health Research Institute, London, ON, Canada

    S. M. Mansour Haeryfar

  4. Division of Clinical Immunology and Allergy, Department of Medicine, Western University, London, ON, Canada

    S. M. Mansour Haeryfar

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  1. S. M. Mansour Haeryfar
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CRS and PTR participated in collection of the relevant literature and in preparation of the manuscript. SMMH conceived the theme and organization of the manuscript, participated in collection of the relevant literature, and wrote the manuscript.

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Correspondence to S. M. Mansour Haeryfar.

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Haeryfar, S.M.M., Shaler, C.R. & Rudak, P.T. Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?. Cancer Immunol Immunother 67, 1885–1896 (2018). https://doi.org/10.1007/s00262-018-2132-1

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