Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25009-4
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Funding
- National Health and Medical Research Council (NHMRC) [1132373, 1113293, 1140406]
- Cancer Council Victoria [APP1143517]
- Priority-driven Collaborative Cancer Research Scheme [1158085]
- Cure Cancer Australia
- National Breast Cancer Foundation Fellowship [ECF-17-005]
- Victorian Cancer Agency Mid-Career Fellowship [MCRF20011]
- Victorian Cancer Agency Early Career Fellowship [ECRF20017]
- NHMRC Senior Research Fellowship [APP1136680]
- NHMRC Senior Principal Research Fellowships [1117766, 1117017]
- NHMRC ECF Fellowship [1160333]
- Australian Research Council [CE140100011]
- National Health and Medical Research Council of Australia [1132373, 1140406, 1160333] Funding Source: NHMRC
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The study reveals that activated MAIT cells can induce an IFN-gamma transcriptome in NK cells and enhance NK-dependent anti-cancer immunity in mice, suggesting a new potential avenue for cancer therapy.
The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-gamma -dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment. Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-gamma transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy.
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