Master of Science
Microbiology and Immunology
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.
Summary for Lay Audience
Mucosa-associated invariant T (MAIT) cells are a subset of immune cells found in high frequencies within mucosal tissues, the ports of microbial entry. When stimulated, MAIT cells quickly orchestrate an immune response against bacterial and viral infections. While their role in antimicrobial immunity is well documented, their functions in cancer immunity are still a subject of on-going investigations. This is because MAIT cells can take on both tumour promoting and tumour inhibiting roles, and which position they take appears to be tissue specific.
To date, the role of MAIT cells in bladder cancer has not been fully investigated. Bladder cancer causes substantial morbidity in human populations and recurrence of the tumour is high with present treatments, calling for an urgent need to develop better treatments. We believe MAIT cells represent attractive targets for the immunotherapy of bladder cancer due to their impressive immunomodulatory properties.
In this thesis study, I uncovered the functional role of MAIT cells in a mouse model of bladder cancer, setting the stage for future experiments to manipulate these cells and bring about desired outcomes.
Using MRI imaging, I found that MAIT enriched mice have greater bladder cancer growth than mice lacking MAIT cells. Analysing the bladder tissues of these mice, I found that MAIT cells take a tumour promoting effector function and that their presence in the bladder is associated with increased frequencies of immune suppressing T regulatory cells. Further investigation and verification on the mechanisms for how MAIT cells participate in bladder cancer immunity can lead to targeted therapies for these mechanisms.
Habaz, Inbar A., "The Role of Mucosa-Associated Invariant T Cells in an Autochthonous Mouse Model of Bladder Cancer" (2023). Electronic Thesis and Dissertation Repository. 9850.
Available for download on Friday, December 19, 2025