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. 2021 Jun 28;13(13):3230. doi: 10.3390/cancers13133230

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Metabolic activities contributing to immune suppression in the tumor microenvironment. Metabolic activities depleting key nutrients include arginine degradation by ARG1 and tryptophan degradation by IDO1/TDO2. Metabolic activities producing immunosuppressive metabolites include 1-MNA production by NNMT, kynurenine synthesis from tryptophan by IDO1/TDO2, D-2HG synthesis by mIDH1/2, adenosine production from ATP/AMP by the combined activities of CD39 and CD73 and production of methylglyoxal by SSAO. CAF: cancer-associated fibroblast; TAM: tumor-associated macrophage; MDSC: myeloid-derived suppressor cell. mIDH: mutant isocitrate dehydrogenase. TDO2: tryptophan-2,3-dioxygenase 2; NNMT: nicotinamide N-methyltransferase; IDO1: indoleamine 2,3 dioxygenase 1; ARG1: arginase 1; SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; SSAO: semicarbazide-sensitive amine oxidase.