Fig. 1: MAIT cell-deficient mice elicit enhanced NK cell-mediated anti-tumor immune responses.

a 2 × 105 B16F10 tumor cells were injected i.v. into B6-MAITcast MR1 WT or B6-MAITcast MR1−/− mice. Lungs were harvested and the number of tumor metastases enumerated 14 days after inoculation. Data is presented as mean ± SEM of n = 26 (B6-MAITcast MR1 WT) or n = 22 (B6-MAITcast MR1−/−) independent mice from four combined experiments, two-tailed Mann–Whitney test. b 3 × 104 B16F10 tumor cells were injected s.c. into B6-MAITcast MR1 WT or B6-MAITcast MR1−/− mice and tumor size monitored. Data is presented as mean ± SEM of n = 10 (B6-MAITcast MR1 WT) or n = 6 (B6-MAITcast MR1−/−) independent mice from a representative experiment of n = 2, Two-way ANOVA. Survival was defined when tumor size exceeded 100 mm2. Data is presented as mean ± SEM of n = 17 (B6-MAITcast MR1 WT) or n = 13 (B6-MAITcast MR1−/−) independent mice from two combined experiments, Log-rank (Mantel-Cox) test. c, d Representative flow cytometry plots (c) and absolute numbers (d) of MAIT (CD45.2+CD19−TCRβ+MR1-5-OP-RU-tetramer+), γδ T (CD45.2+CD19−TCRγδ+), NKT (CD45.2+CD19−TCRβ+αGalCer-tetramer+), myeloid (CD45.2+CD19−CD11b+Ly6C+), conventional T (Tconv; CD45.2+CD19−TCRβ+) and CD4+ and CD8+ T cells in the lungs of indicated mice. Data is presented as mean ± SEM of n = 7 (C57BL/6) and n = 10 (B6-MAITcast MR1 WT) independent mice from three combined experiments (MAIT cells), or n = 6 (B6-MAITcast MR1 WT) and n = 5 (B6-MAITcast MR1−/−) independent mice from two combined experiments (γδ T cells, NKT cells), or n = 11 independent mice from three combined experiments (CD11b+Ly6C+ myeloid cells), or n = 11 (B6-MAITcast MR1 WT) and n = 10 (B6-MAITcast MR1−/−) independent mice from three combined experiments (conventional T cells, CD4+ T cells, CD8+ T cells), two-tailed Mann–Whitney test. Numbers shown in MAIT cells panel indicate the proportion of MAIT cells (red gate) from TCRβ+ gate (grey gate). e Absolute number and phenotype of NK cells (CD19−TCRβ−NK1.1+) and CD11b/CD27 profile from lungs of B6-MAITcast MR1 WT or B6-MAITcast MR1−/− mice. Data is presented as mean ± SEM of n = 19 (B6-MAITcast MR1 WT) and n = 20 (B6-MAITcast MR1−/−) independent mice from five combined experiments, two-tailed Mann–Whitney test (left) and n = 6 (B6-MAITcast MR1 WT) or n = 7 (B6-MAITcast MR1−/−) independent mice from two combined experiments, Two-way ANOVA (right). f B16F10 tumor cells were inoculated into B6-MAITcast MR1 WT or B6-MAITcast MR1−/− mice as per a and NK cells depleted with anti-asialo GM-1 (αASGM1) on days -1 and 0. Data is presented as mean ± SEM of n = 8 (untreated B6-MAITcast MR1 WT), n = 9 (untreated B6-MAITcast MR1−/−), n = 6 (anti-asialo GM-1 treated B6-MAITcast MR1 WT) and n = 5 (anti-asialo GM-1 treated B6-MAITcast MR1−/−) independent mice and is representative of two independent experiments, One-way ANOVA. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns = non-significant.