Electronic Thesis and Dissertation Repository

The Role of Mucosa-Associated Invariant T Cells in an Autochthonous Mouse Model of Bladder Cancer

Inbar A. Habaz

Abstract

Mucosa-associated invariant T (MAIT) cells are enriched in mucosal layers and exhibit both tumour promoting and inhibiting functions against mucosal cancers. Yet whether MAIT cells promote or fight against bladder cancer (BC) has been unclear. Using magnetic resonance imaging, we compared BC burden induced by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine between MAIT enriched B6-MAITCAST mice and their MAIT deficient (Mr1-/-) counterparts. My findings show MAIT enriched mice have greater tumour burden, suggesting a detrimental role for steady-state MAIT cells in BC progression. Furthermore, cytofluorimetric analyses revealed that MAIT cells in BC were biased towards RAR-related orphan receptor γt (RORγt), Forkhead box P3 (FOXP3), and Tumour necrosis factor-α (TNF-α) expression, proteins known to have cancer promoting capabilities. We also found the presence of MAIT cells to associate with increased frequencies of immune suppressing T regulatory cells in the bladder. I propose that MAIT cells constitute attractive targets for the immunotherapy of BC.