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. 2021 Jun 10;11:693517. doi: 10.3389/fonc.2021.693517

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Copyright © 2021 Tan, Wang, Zhang, Ge, Zhong, Xia and Sun

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(s) 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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Origin and Heterogeneity of TAMs. Macrophages in tumors actually have at least three sources, including bone marrow, fetal liver and embryonic yolk sac. Bone-marrow-derived macrophages (BMDMs) develop from hematopoietic stem cells in the bone marrow, while tissue-resident macrophages (TRMs) develop from erythro-myeloid progenitors in the fetal liver or embryonic yolk sac. TAMs can differentiate into various phenotypes upon stimulation by different signals in the tumor microenvironment, and the protumor and antitumor phenotypes are the two extremes of the spectrum.