Obesity is a chronic and progressive disease which impacts over 1 billion individuals globally. Obesity can have a significant impact on an individual’s health due to increased prevalence and (or) severity of numerous co-morbidities. A major concern is the association of obesity with an increased risk of 12 specific cancers. Mucosal Associated Invariant T (MAIT) cells are a subset of unconventional T cells that are emerging as potent anti-cancer effectors. These protective effects are underpinned by their production of anti-cancer molecules such as interferon gamma (IFNg), granzyme B and the ability to directly kill cancerous target cells. Previous work from the lab of my proposed mentor has reported significant defects in MAIT cells in the setting of obesity, however the impact of obesity on MAIT cell anti-cancer responses have not been reported to date. In my proposed project I will first test the anti-cancer activity of MAIT cells against a range of obesity-related cancer targets (e.g. colorectal cancer). Then I will perform cross-sectional analysis of MAIT cell anti-cancer activity in cohorts of people living with obesity (PWO) and non-obesity controls using state-of-the-art single approaches including multi-colour flow cytometric analysis and target-cell killing assays.
