For an infiltrating cytotoxic T cell, entering the tumor microenvironment is like taking up arms in the desert: due to the highly energetic nature of tumor cells, the tumor microenvironment has poor metabolite availability. How can a T cell be expected to kill tumor cells without any food to fuel them?

Our lab is exploring ways to metabolically remodel the tumor microenvironment to provide more fuel for T cell function. We have recently shown mitochondrial complex I inhibitor Metformin can decrease oxygen consumption in tumor cells. Metformin, when combined with checkpoint blockade therapy, dramatically decreases tumor burden in preclinical cancer models. Our findings are now being translated to clinical trials to help improve immunotherapy in cancer patients.