RT Journal Article
SR Electronic
T1 A pan-cancer metabolic atlas of the tumor microenvironment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.16.342519
DO 10.1101/2020.10.16.342519
A1 Rohatgi, Neha
A1 Ghoshdastider, Umesh
A1 Baruah, Probhonjon
A1 Skanderup, Anders Jacobsen
YR 2020
UL http://biorxiv.org/content/early/2020/10/16/2020.10.16.342519.abstract
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.