Oral Presentation Melbourne Immunotherapy Network Winter Retreat 2018

Investigating the role of Mucosal-Associated Invariant T (MAIT) cells in cancer (#39)

Emma V Petley 1 , Hui-Fern Koay 2 , Kirsten Todd 1 , Melissa Henderson 1 , David P Fairlie 3 , Jeffrey Mak 3 , Ligong Liu 3 , Nicholas Gherardin 2 , Dale Godfrey 2 , Phil Darcy 1 , Paul Beavis 1
  1. Peter MacCallum Cancer Centre, Brunswick East, VIC, Australia
  2. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Brunswick East, Victoria, Australia
  3. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, Brisbane, QLD, Australia

The success of immunotherapies such as checkpoint blockade in patients 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. However, it is unclear whether MAIT cells contribute to anti-tumour immune responses, although previously we have shown they are capable of cytotoxic activity against multiple myeloma lines1. To extend these studies to an in vivo setting, we first compared anti-tumour responses in a B16F10 lung metastasis model where tumour cells were loaded with 5-OP-RU, a potent MAIT cell agonist. Strikingly, given the low frequency of MAIT cells in C57/BL6 mice we observed a significant decrease in lung metastasis, compared to unloaded tumour cells. Interestingly, in the primary tumour setting, intratumoural injections of MAIT cell ligands into B16F10 tumours did not affect tumour growth. These results suggest that MAIT cells have the potential to control tumour metastasis, but play a limited role in the primary tumour setting.

  1. 1. Gherardin NA, Loh L, Admojo L, et al. Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma. Scientific Reports. March 2018:1-14. doi:10.1038/s41598-018-22130-1.