MAIT cells regulate NK cell-mediated tumor immunity

Emma Petley; Hui-Fern Koay; Melissa A Henderson; Kevin Sek; Kirsten L Todd; Simon P Keam; Junyun Lai; Imran G House; Jasmine Li; Magnus Zethoven; Amanda XY Chen; Amanda J Oliver; Jessica Michie; Andrew J Freeman; Lauren Giuffrida; Jack D Chan; Angela Pizzolla; Jeffrey YW Mak; Timothy R McCulloch; Fernando Souza-Fonseca-Guimaraes; Conor J Kearney; Rosemary Millen; Robert G Ramsay; Nicholas D Huntington; James McCluskey; Jane Oliaro; David P Fairlie; Paul J Neeson; Dale Godfrey; Paul A Beavis; Phillip K Darcy

Journal article

MAIT cells regulate NK cell-mediated tumor immunity

Emma Petley, Hui-Fern Koay, Melissa A Henderson, Kevin Sek, Kirsten L Todd, Simon P Keam, Junyun Lai, Imran G House, Jasmine Li, Magnus Zethoven, Amanda XY Chen, Amanda J Oliver, Jessica Michie, Andrew J Freeman, Lauren Giuffrida, Jack D Chan, Angela Pizzolla, Jeffrey YW Mak, Timothy R McCulloch, Fernando Souza-Fonseca-Guimaraes Show all

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2021

DOI: 10.1038/s41467-021-25009-4

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Abstract

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 incre..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Conor Kearney Author The Sir Peter Maccallum Department of Oncology

Phillip Darcy Author The Sir Peter Maccallum Department of Oncology

Angela Pizzolla Author The Sir Peter Maccallum Department of Oncology

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Cancer Council Victoria

Awarded by Priority-driven Collaborative Cancer Research Scheme

Awarded by National Breast Cancer Foundation Fellowship

Awarded by Victorian Cancer Agency Mid-Career Fellowship

Awarded by Victorian Cancer Agency Early Career Fellowship

Awarded by NHMRC Senior Research Fellowship

Awarded by NHMRC Senior Principal Research Fellowships

Awarded by NHMRC ECF Fellowship

Awarded by Australian Research Council

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

The authors would like to acknowledge the assistance of the Animal Facility technicians at the Peter MacCallum Cancer Centre and Prof. Olivier Lantz for the provision of B6-MAITcast mice. This work was funded by Program Grants from the National Health and Medical Research Council (NHMRC; 1132373, 1113293, and 1140406) and a Cancer Council Victoria grant (APP1143517). F.S.F.G received a grant #1158085 awarded through the Priority-driven Collaborative Cancer Research Scheme and funded by Cure Cancer Australia with the assistance of Cancer Australia. P.A.B. was supported by National Breast Cancer Foundation Fellowship (ID# ECF-17-005, 2016-2020) and a Victorian Cancer Agency Mid-Career Fellowship (MCRF20011, 2021-current). I.G. House is supported by a Victorian Cancer Agency Early Career Fellowship (ECRF20017). P.K.D. is supported by an NHMRC Senior Research Fellowship (APP1136680). D.I.G. and F.P.F. are supported by NHMRC Senior Principal Research Fellowships (1117766, 1117017). H.-F.K. is supported by an NHMRC ECF Fellowship (1160333); D.I.G., H-F.K., J.Y.W.M., and D.P.F. are also supported by the Australian Research Council CE140100011.