MAIT cells promote tumor initiation, growth and metastases via tumor MR1

J Yan; S Allen; E McDonald; I Das; JYW Mak; L Liu; DP Fairlie; BS Meehan; Z Chen; AJ Corbett; A Varelias; MJ Smyth; MWL Teng

Journal article

MAIT cells promote tumor initiation, growth and metastases via tumor MR1

J Yan, S Allen, E McDonald, I Das, JYW Mak, L Liu, DP Fairlie, BS Meehan, Z Chen, AJ Corbett, A Varelias, MJ Smyth, MWL Teng

Cancer Discovery | AMER ASSOC CANCER RESEARCH | Published : 2020

DOI: 10.1158/2159-8290.CD-19-0569

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that require MHC class I-related protein 1 (MR1) for their development. The role of MAIT cells in cancer is unclear and to date, no study has evaluated these cells in vivo in this context. Here, we demonstrated that tumor initiation, growth and experimental lung metastasis were significantly reduced in MR1-/- mice, compared with WT mice. The anti-tumor activity observed in MR1-/- mice required NK and/or CD8+ T cells and IFNy. Adoptive transfer of MAIT cells into MR1-/- mice reversed metastasis reduction. Similarly, MR1 blocking antibodies decreased lung metastases and suppressed tumor growth. Following MR1 ligand exposure so..

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University of Melbourne Researchers

Bronwyn Meehan Author

Zhenjun Chen Author

Alexandra Corbett Author

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Grants

Awarded by Tizona Therapeutics

Funding Acknowledgements

The authors thank Liam Town, Kate Elder, Brodie Quine, and Gabrielle Kelly for breeding and genotyping of mice throughout this study. We would also like to thank Glen Boyle and Frank Vari for kindly providing human tumor cell lines, and Sebastien Jacquelin and Xian Yang Li for CRISPR/Cas9 technical assistance. We would also like to thank Dillon Corvino, Venkateswar Addala, and John Stagg for their intellectual input and helpful discussions. M.J. Smyth was supported by an NH&MRC Research Fellowship (1078671). W.L. Teng was supported by an NH&MRC CDF Fellowship (1159655). J. Yan was supported by a University of Queensland International Scholarship co-funded by QIMR Berghofer. A.J. Corbett is supported by an ARC Future Fellowship (FT160100083). D.P. Fairlie is supported by an NH&MRC Senior Principal Research Fellowship (1117017) and an ARC Centre of Excellence grant (CE140100011).