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 some, but not all, mouse and human tumor cell lines up-regulated MR1. Pre-treatment of tumor cells with the stimulatory ligand 5-OP-RU or inhibitory ligand Ac-6-FP increased or decreased lung metastases, respectively. MR1-deleted tumors resulted in fewer metastases compared with parental tumor cells. MAIT cell suppression of NK cell effector function was tumor-MR1-dependent and partially required IL-17A. Our studies indicate that MAIT cells display tumor promoting function by suppressing T and/or NK cells and that blocking MR1 may represent a new therapeutic strategy for cancer immunotherapy.
|Authors||Yan, Juming; Allen, Stacey; McDonald, Elizabeth; Das, Indrajit; Mak, Jeffrey Y W; Liu, Ligong; Fairlie, David P; Meehan, Bronwyn S; Chen, Zhenjun; Corbett, Alexandra J; Varelias, Antiopi; Smyth, Mark J; Teng, Michele W L|
|Funding Body||NH&MRC Research Fellowship|