The ability of immunomodulators like anti-PD1 and anti-CTLA4 to enhance the immunologic response to cancer has provided benefit to patients with a wide variety of cancers. These therapies are most effective in tumors with a high mutational burden, but it is still only a minority of solid tumor patients who benefit from current immunotherapies. This is in part due to the ability of tumors to employ additional strategies to silence an immune response. One of the most potent immunosuppressive mechanisms tumors exploit is the depletion of specific metabolites from the tumor environment. We have explored the effects of such depletions on T cell effector function. The results suggest that therapies to alter tumor metabolism should be combined to checkpoint blocking agents to optimize immuno-oncology therapy.