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Review
. 2018 May;24(5):472-489.
doi: 10.1016/j.molmed.2018.03.006. Epub 2018 Apr 11.

Macrophages: The Road Less Traveled, Changing Anticancer Therapy

Jennifer L Guerriero  1
Affiliations
Review

Macrophages: The Road Less Traveled, Changing Anticancer Therapy

Jennifer L Guerriero. Trends Mol Med. 2018 May.

Abstract

Macrophages are present in all vertebrate tissues and have emerged as multifarious cells with complex roles in development, tissue homeostasis, and disease. Macrophages are a major constituent of the tumor microenvironment, where they either promote or inhibit tumorigenesis and metastasis depending on their state. Successful preclinical strategies to target macrophages for anticancer therapy are now being evaluated in the clinic and provide proof of concept that targeting macrophages may enhance current therapies; however, clinical success has been limited. This review discusses the promise of targeting macrophages for anticancer therapy, yet highlights how much is unknown regarding their ontogeny, regulation, and tissue-specific diversity. Further work might identify subsets of macrophages within different tissues, which could reveal novel therapeutic opportunities for anticancer therapy.

Keywords: CSF-1R; novel anticancer therapy; tumor microenvironment; tumor-associated macrophages.

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Figures

Figure 1
Figure 1. The road of macrophage ontogeny in tissue
Macrophages in tissues arise from at least 3 distinct sources. During primitive hematopoiesis macrophages arise from the YS independent of HSC precursors and populate the brain, constituting the major brain macrophage lineage, microglia. Additionally, the fetal liver is populated with YS-derived macrophages and become the major source of tissue resident macrophages (TRM) in the lung, spleen, liver, pancreas and kidney. Bone-marrow derived macrophages (BDM) constitute yet a third source of macrophages, which can populate all major organs upon homeostatic adaptations, infection, disease or cancer.
Figure 2
Figure 2. The cellular ontogeny of TAMs
TRM are derived from yolk-sac and fetal liver progenitors, which can proliferate in some tumors and have been shown to promote tumorigenesis in brain and pancreatic cancer. Hematopoietic stem cells of the bone marrow give rise to monocytes which can populate tumors and have been shown to promote tumorigenesis in breast and lung cancer.
Figure 3
Figure 3
Current strategies to target tumor associated macrophages for anti-cancer therapy.
See this image and copyright information in PMC

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