We and others have found that local nutrient availability can significantly alter cellular function and identity by effecting changes in the concentrations of intracellular metabolites (Vardhana et al, Nat Metabolism 2019). We aim to understand how this modifies T-cell function in vivo:
- How does nutrient availability in vivo affect intratumoral T-cell metabolism?
- How is local nutrient availability affected by tumor stromal composition, tissue residence, and organismal metabolic state?
- Can nutrient sensing by T-cells in vivo be inferred by their transcriptional or epigenetic state?
To answer these questions, we have developed both novel mouse models to track immune responses across distinct cells of origin and tissue residence as well as rapid, high-sensitivity protocols to assess nutrient uptake and utilization from individual cell types within tumors.