remodeling TIL metabolism to improve immunotherapy

mTOR restricts Antitumor Immunity. In states of nutrient availability, the energy sensor mTOR stimulates anabolic metabolism that generates glycoATP and activates protein translation (23). Preliminary data generated in the lab prompted us to test whether the metabolic energy sensor mTOR restricts T cell translation in tumors. We measured the ability of T cells to make protein in the tumor microenvironment in the presence of mTOR inhibitor Rapamycin (Rapa) (24). Rapa-treated T cells showed reduced glycoATP and increased translation in the tumor microenvironment (Fig. 6A-C). These data agreed with our preliminary findings that glycolysis restricts T cell translation in tumors. Transfer of Rapa conditioned T cells produced robust tumor regression of B16F1-OVA melanomas (Fig 6D). The data show that mTOR mars antitumor immunity. 

Remodeling Fig.tiff