PT  - JOURNAL ARTICLE
AU  - Neha Rohatgi
AU  - Umesh Ghoshdastider
AU  - Probhonjon Baruah
AU  - Anders Jacobsen Skanderup
TI  - A pan-cancer metabolic atlas of the tumor microenvironment
AID  - 10.1101/2020.10.16.342519
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.16.342519
4099  - http://biorxiv.org/content/early/2020/10/16/2020.10.16.342519.short
4100  - http://biorxiv.org/content/early/2020/10/16/2020.10.16.342519.full
AB  - 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 StatementThe authors have declared no competing interest.