GLUTAMINE AVAILABILITY REGULATES TISSUE-SPECIFIC CDC SUBSETS

Proliferating tumor cells import glutamine for anabolic processes, engendering glutamine deficiency in the tumor microenvironment. How this impacts immune cells is not well understood. Using multiple mouse models of soft tissue sarcomas, glutamine antagonists, as well as genetic and pharmacological inhibition of glutamine utilization, we determined that the number and frequency of conventional dendritic cells type 1 (cDC1s) is dependent on microenvironmental glutamine concentrations. Low glutamine levels provoke cDC1 deficiency by reducing proliferation and survival of mature cDC1s but not their progenitors. Notably, this glutamine dependence was observed in tumors, normal tissues, and in vitro systems of DC-poiesis, but not in splenic cDC1s. Further studies suggest a role of the nutrient sensing mTORC1 signaling pathway in this process. Taken together, these findings uncover a tissue-specific dependence of cDC subsets on glutamine availability that is coopted by tumors to escape immune responses.