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MAIT cells regulate NK cell-mediated tumor immunity

Author

Listed:
  • Emma V. Petley

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Hui-Fern Koay

    (University of Melbourne
    University of Melbourne)

  • Melissa A. Henderson

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Kevin Sek

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Kirsten L. Todd

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Simon P. Keam

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Junyun Lai

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Imran G. House

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Jasmine Li

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Magnus Zethoven

    (The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Amanda X. Y. Chen

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Amanda J. Oliver

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Jessica Michie

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Andrew J. Freeman

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Lauren Giuffrida

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Jack D. Chan

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Angela Pizzolla

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Jeffrey Y. W. Mak

    (The University of Queensland
    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
    The University of Melbourne)

  • Rosemary Millen

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Robert G. Ramsay

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Nicholas D. Huntington

    (University of Melbourne
    Walter and Eliza Hall Institute of Medical Research
    Monash University)

  • James McCluskey

    (University of Melbourne)

  • Jane Oliaro

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Monash University)

  • David P. Fairlie

    (The University of Queensland
    The University of Queensland)

  • Paul J. Neeson

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Dale I. Godfrey

    (University of Melbourne
    University of Melbourne)

  • Paul A. Beavis

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    University of Melbourne)

  • Phillip K. Darcy

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Monash University
    University of Melbourne)

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.

Suggested Citation

  • 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 , 2021. "MAIT cells regulate NK cell-mediated tumor immunity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25009-4
    DOI: 10.1038/s41467-021-25009-4
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    Cited by:

    1. Cameron, Anna & Khanal, Mukesh & Tedds, Lindsay M., 2022. "Managing Airbnb: A Cross-Jurisdictional Review of Approaches for Regulating the Short-Term Rental Market," MPRA Paper 111535, University Library of Munich, Germany.

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