T cells play important roles in cancer immunosurveillance and anti-tumor immunity. Metabolic constraints in the tumor microenvironment can negatively impact anti-tumor T cell responses, in part by competition of tumor infiltrating lymphocytes (TIL) with tumor cells for available nutrients such as glucose. Engagement of receptors such as PD-1 on activated T cells reduces T cell responsiveness and promotes T cell “exhaustion”.
Our work is focused on understanding the metabolic constraints that the tumour microenvironment impose on T cell expansion and function, and whether we can reverse the negative effects of the tumour microenvironment on T cells to enhance anti-tumour immunity. We are particularly interested in the role that metabolic sensors such as AMPK play in this process, and whether metabolic interventions can work in concert with immunotherapy techniques (i.e. checkpoint blockade therapy) to promote anti-tumour immune responses.