Unraveling the immunotherapy obesity paradox in triple-negative breast cancer

Breast cancer is the most common cancer in women. Triple-negative breast cancer (TNBC) is particularly difficult to treat due to a lack of typical treatment targets. Obesity is linked to higher incidence of TNBC and worse cancer progression; as obesity rates rise, it is important to consider the effects of obesity on TNBC.
Cancer cells evade the immune system by deactivating immune cells. Anti-PD-1 drugs restore immune response against tumours, but most patients do not experience a benefit. Paradoxically, recent research suggests that obesity enhances anti-PD-1 therapy.
We will investigate the effects of obesity on lipid utilization in TNBC tumour and immune cells and anti-PD-1 effectiveness. We hypothesize that obesity will enhance anti-PD-1 and studying changes in lipid usage in tumour and immune cells will reveal mechanisms responsible for increased anti-PD-1 effectiveness. Mice will be fed a regular or high-fat diet and implanted with TNBC cells into mammary fat tissue. We will compare lipid profiles in the tumour and immune cells of lean versus obese mice and evaluate anti-PD-1 efficacy. By studying how obesity alters lipid metabolism in TNBC, we will uncover mechanisms responsible for modulating anti-PD-1 effectiveness.