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. 2021 Apr 14;10(4):903. doi: 10.3390/cells10040903

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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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The metabolic regulation of TAMs’ ontogeny. Embryonic TRMs in the peritoneum display decreased glycolysis and increased OXPHOS compared with monocyte-derived peritoneal macrophages due to mTORC2/FOXO1 axis. Higher FOXO1 expression is also observed in other TRMs (in the lung, spleen, skin, and liver) compared with MDMs, indicating this metabolic bias’s tissue universality. Embryonic TRMs and bone marrow MDMs constitute TAM pools in various tumor types. The metabolic imprints in TAMs from different origins may play an essential role in TAM heterogeneity. TRMs: tissue-resident macrophages; MDMs: monocyte-derived macrophages. TAMs: tumor-associated macrophages.