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Targeting MAITs as an Opportunity Beyond Weight Loss for Solving the Public Health Crisis of Obesity-associated Cancer – thinking outside the box by looking inside the adipose tissue

Obesity is a global epidemic and the number of people living with obesity continues to increase despite decades-long campaigning to eat less and move more. People with obesity(PWO) are at a higher risk of cancer, and although this is known there have not been any successful attempts to reduce obesity-associated cancer(OAC) at a societal level. This is because of the simplistic approach of weight management for risk reduction, when in reality the situation is much more complex with many more opportunities for intervention. Successfully reducing the risk of cancer in PWO will require research and collaboration. I propose to investigate the biology of how obesity-induced immune dysfunction contributes to cancer. Specifically, I will focus on a particular type of immune cell, called a MAIT because I have previously shown that it is excellent at killing cancer cells in the laboratory. I have also shown that PWO have fewer MAITs, that their MAITs are not good at killing cancer cells (Figure2), and that instead MAITs from PWO actually contribute to inflammation which increases cancer risk. How MAITs can behave so differently in PWO to those from people without obesity is unknown. I have looked at the behaviour of fat cells from PWO(fat samples donated during surgery), and found that they express proteins specifically recognised by MAITs. I therefore want to study this interaction, work which will require world-leading technology available at Karolinska Institute(KI), and surgical adipose samples available from a clinical collaboration at Maynooth University(MU). I believe that the findings could contribute to public health policy and / or new treatments help reduce illness and death from OAC, for example by issuing targeted public health advice, or by generating a MAIT-based cellular therapy. I will work at a cellular therapy company(ONK Therapeutics) on secondment to assess the potential of the latter.