Journal article

MAIT Cells Promote Tumor Initiation, Grow and Metastases via Tumor MR1

Juming Yan, Stacey Allen, Elizabeth McDonald, Indrajit Das, Jeffrey YW Mak, Ligong Liu, David P Fairlie, Bronwyn S Meehan, Zhenjun Chen, Alexandra J Corbett, Antiopi Varelias, Mark J Smyth, Michele WL Teng



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 wild-type mice. The antitumor activity observed in Mr1 -/- mice required natural killer (NK) and/or CD8+ T cells and IFNγ. Adoptive transfer of MAIT cells into Mr1 -/- mice reversed metastasis reduction. Similarly, MR1-blocking antibodies decreased lung metastases and suppressed tumor growth. Follo..

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Awarded by NH&MRC Research Fellowship

Awarded by NH&MRC CDF Fellowship

Awarded by ARC Future Fellowship

Awarded by NH&MRC Senior Principal Research Fellowship

Awarded by ARC Centre of Excellence

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).