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. Following MR1 ligand exposure, some, but not all, mouse and human tumor cell lines upregulated MR1. Pretreatment 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 IL17A. 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. SIGNIFICANCE: Contradicting the perception that MAIT cells kill tumor cells, here MAIT cells promoted tumor initiation, growth, and metastasis. MR1-expressing tumor cells activated MAIT cells to reduce NK-cell effector function, partly in a host IL17A-dependent manner. MR1-blocking antibodies reduced tumor metastases and growth, and may represent a new class of cancer therapeutics.This article is highlighted in the In This Issue feature, p. 1.

中文翻译：

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MAIT 细胞通过肿瘤 MR1 促进肿瘤的发生、生长和转移。

粘膜相关不变性 T (MAIT) 细胞是先天样 T 细胞，其发育需要 MHC I 类相关蛋白 1 (MR1)。MAIT 细胞在癌症中的作用尚不清楚，迄今为止，还没有研究在这种情况下对这些细胞进行体内评估。在这里，我们证明了与野生型小鼠相比，Mr1 -/- 小鼠的肿瘤起始、生长和实验性肺转移显着减少。在 Mr1 -/- 小鼠中观察到的抗肿瘤活性需要自然杀伤 (NK) 和/或 CD8+ T 细胞和 IFNγ。MAIT 细胞过继转移到 Mr1 -/- 小鼠逆转了转移减少。同样，MR1 阻断抗体可减少肺转移并抑制肿瘤生长。在 MR1 配体暴露后，一些（但不是全部）小鼠和人类肿瘤细胞系上调了 MR1。用刺激性配体 5-OP-RU 或抑制性配体 Ac-6-FP 预处理肿瘤细胞分别增加或减少肺转移。与亲本肿瘤细胞相比，MR1 缺失的肿瘤导致更少的转移。MAIT 细胞对 NK 细胞效应器功能的抑制是肿瘤 MR1 依赖性的，部分需要 IL17A。我们的研究表明，MAIT 细胞通过抑制 T 和/或 NK 细胞显示出促进肿瘤的功能，并且阻断 MR1 可能代表了癌症免疫治疗的新治疗策略。意义：与 MAIT 细胞杀死肿瘤细胞的看法相反，这里 MAIT 细胞促进了肿瘤的发生、生长和转移。表达 MR1 的肿瘤细胞激活 MAIT 细胞以降低 NK 细胞效应器功能，部分以宿主 IL17A 依赖性方式。MR1 阻断抗体减少肿瘤转移和生长，并且可能代表一类新的癌症疗法。这篇文章在本期专题中突出显示，第。1.