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. 2018 Jan 29;9:40. doi: 10.3389/fimmu.2018.00040

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Copyright © 2018 Sormendi and Wielockx.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematic representation of amino acid metabolism in different cell types. Cancer cells (CCs: orange), cancer-associated fibroblasts (CAFs: brown), myeloid-derived suppressor cells (MDSCs: purple), as well as M2 macrophages (blue) show increased expression of arginase, depleting the surrounding environment of arginine, which is essential for TCR activation in T cells (green). Ornithine coming from arginase metabolism also dampens T cell activation. Moreover, increased expression of indoleamine-2,3-dioxygenase (IDO) in CC and MDSCs favors catabolism of tryptophan into kyneurine, with immune suppressive effects. In addition, overexpression of GLS via HIF/c-Myc regulation in CA, CAFs, MDSCs, and endothelial cells (ECs: pink) generates glutamate, which is used to replenish intermediates of the TCA cycle, favoring FA synthesis from citrate.