ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

MAIT cells regulate NK cell mediated tumor immunity (#135)

Emma Petley 1 2 , Hui-Fern Koay 3 4 , Melissa A Henderson 1 2 , Kevin Sek 1 2 , Kirsten L Todd 1 2 , Simon P Keam 1 2 5 , Junyun Lai 1 2 , Imran G House 1 2 , Jasmine Li 1 2 , Magnus Zethoven 2 6 , Amanda X.Y Chen 1 2 , Amanda J Oliver 1 2 , Jessica Michie 1 2 , Andrew J Freeman 1 2 , Lauren Giuffrida 1 2 , Jack D Chan 1 2 , Angela Pizzolla 1 2 , Jeffrey Y.W. Mak 7 8 , Timothy R McCulloch 9 , Fernando Guimaraes 9 , Conor J Kearney 1 2 , Rosemary Millen 1 2 , Robert G Ramsay 1 2 , Nicholas D Huntington 10 11 12 , James McCluskey 3 , Jane Oliaro 1 2 13 , David P Fairlie 7 8 , Paul J Neeson 1 2 , Dale I Godfrey 3 4 , Paul A Beavis 1 2 14 , Phil K Darcy 1 2 12 14
  1. Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
  3. Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  4. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Victoria, Australia
  5. Tumour Suppression and Cancer Sex Disparity Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  6. Bioinformatics Core Facility, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  7. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  8. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Queensland, Brisbane, QLD, Australia
  9. University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia
  10. Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
  11. Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  12. Biomedicine Discovery Institute and the Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia
  13. Department of Immunology, Monash University, Melbourne, Victoria, Australia
  14. Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia

The success of immunotherapies, such as checkpoint blockade, has highlighted the importance of the immune system in controlling tumours. The presence of conventional T cells within the tumour microenvironment have been intensively studied and correlates with patient outcomes, however, the role of mucosal-associated invariant T (MAIT) cells in cancer is relatively unknown.  MAIT cells are abundant in humans and enriched in mucosal tissues, such as the colon and lung, and some recent studies have reported the presence of these cells within primary and metastatic tumours. Our recent publication1 shows that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumour growth relative to control mice. Analyses of this interplay in human tumour samples revealed that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumours with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumour immunity in B16F10 and E0771 mouse tumour models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFNγ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumour samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, suggesting a potential therapeutic avenue for cancer treatment

 

  1. Petley, E. V., Koay, H. F., Henderson, M. A., Sek, K., Todd, K. L., Keam, S. P., . . . Darcy, P. K. (2021). MAIT cells regulate NK cell-mediated tumor immunity. Nat Commun, 12(1), 4746. doi:10.1038/s41467-021-25009-4