MAIT cells regulate NK cell-mediated tumor immunity

Emma V. 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 X. Y. Chen, Amanda J. Oliver, Jessica Michie, Andrew J. Freeman, Lauren Giuffrida, Jack D. Chan, Angela Pizzolla, Jeffrey Y. W. 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 I. Godfrey (), Paul A. Beavis () and Phillip K. Darcy ()
Additional contact information
Emma V. Petley: Peter MacCallum Cancer Centre
Hui-Fern Koay: University of Melbourne
Melissa A. Henderson: Peter MacCallum Cancer Centre
Kevin Sek: Peter MacCallum Cancer Centre
Kirsten L. Todd: Peter MacCallum Cancer Centre
Simon P. Keam: Peter MacCallum Cancer Centre
Junyun Lai: Peter MacCallum Cancer Centre
Imran G. House: Peter MacCallum Cancer Centre
Jasmine Li: Peter MacCallum Cancer Centre
Magnus Zethoven: The University of Melbourne
Amanda X. Y. Chen: Peter MacCallum Cancer Centre
Amanda J. Oliver: Peter MacCallum Cancer Centre
Jessica Michie: Peter MacCallum Cancer Centre
Andrew J. Freeman: Peter MacCallum Cancer Centre
Lauren Giuffrida: Peter MacCallum Cancer Centre
Jack D. Chan: Peter MacCallum Cancer Centre
Angela Pizzolla: Peter MacCallum Cancer Centre
Jeffrey Y. W. Mak: The University of Queensland
Timothy R. McCulloch: University of Queensland Diamantina Institute, The University of Queensland
Fernando Souza-Fonseca-Guimaraes: University of Queensland Diamantina Institute, The University of Queensland
Conor J. Kearney: Peter MacCallum Cancer Centre
Rosemary Millen: Peter MacCallum Cancer Centre
Robert G. Ramsay: Peter MacCallum Cancer Centre
Nicholas D. Huntington: University of Melbourne
James McCluskey: University of Melbourne
Jane Oliaro: Peter MacCallum Cancer Centre
David P. Fairlie: The University of Queensland
Paul J. Neeson: Peter MacCallum Cancer Centre
Dale I. Godfrey: University of Melbourne
Paul A. Beavis: Peter MacCallum Cancer Centre
Phillip K. Darcy: Peter MacCallum Cancer Centre

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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 increased expression of both IFN-γ-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.

Date: 2021
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DOI: 10.1038/s41467-021-25009-4

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