A pan-cancer metabolic atlas of the tumor microenvironment

Tumors are heterogeneous cellular environments with entwined metabolic dependencies. Here, we used a tumor transcriptome deconvolution approach to profile the metabolic states of cancer and non-cancer (stromal) cells in bulk tumors of 20 solid tumor types. We identified metabolic genes and processes recurrently altered in cancer cells across tumor types, including pan-cancer upregulation of deoxythymidine triphosphate (dTTP) production. In contrast, the tryptophan catabolism rate limiting enzymes, IDO1 and TDO2 , were highly overexpressed in stroma, suggesting that kynurenine-mediated suppression of antitumor immunity is predominantly constrained by the stroma. Oxidative phosphorylation was unexpectedly the most upregulated metabolic process in cancer cells compared to both stromal cells and a large atlas of cancer cell lines, suggesting that the Warburg effect may be less pronounced in cancer cells in vivo . Overall, our analysis highlights fundamental differences in metabolic states of cancer and stromal cells inside tumors and establishes a pan-cancer resource to interrogate tumor metabolism. ### Competing Interest Statement The authors have declared no competing interest.