Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 2;9(4):374.
doi: 10.3390/biomedicines9040374.

Tumor-Associated Macrophages-Implications for Molecular Oncology and Imaging

Melanie A Kimm  1 , Christopher Klenk  1 , Marianna Alunni-Fabbroni  1 , Sophia Kästle  1 , Matthias Stechele  1 , Jens Ricke  1 , Michel Eisenblätter  2 , Moritz Wildgruber  1
Affiliations
Review

Tumor-Associated Macrophages-Implications for Molecular Oncology and Imaging

Melanie A Kimm et al. Biomedicines. .

Abstract

Tumor-associated macrophages (TAMs) represent the largest group of leukocytes within the tumor microenvironment (TME) of solid tumors and orchestrate the composition of anti- as well as pro-tumorigenic factors. This makes TAMs an excellent target for novel cancer therapies. The plasticity of TAMs resulting in varying membrane receptors and expression of intracellular proteins allow the specific characterization of different subsets of TAMs. Those markers similarly allow tracking of TAMs by different means of molecular imaging. This review aims to provides an overview of the origin of tumor-associated macrophages, their polarization in different subtypes, and how characteristic markers of the subtypes can be used as targets for molecular imaging and theranostic approaches.

Keywords: macrophages; molecular imaging; monocytes; polarization; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Functional hallmarks of M1 and M2 TAMs.
Figure 2
Figure 2
Monocyte recruitment and TAM polarization during tumor development and therapy. Monocytes from different compartments (bone marrow, blood, spleen) are directed to the tumor microenvironment (TME) via secreted factors and exosomes. Here, they differentiate into TAMs of different subtypes (M1/M2). Therapies leading to the repolarization of M2 TAMs into M1 TAMs or monocytes are promising strategies for tumor destruction.
Figure 3
Figure 3
TAM tracking using optical imaging. (A–C) DiR-labeled macrophages (B), directly tracked 48 h after intravenous application using FRI (A) and FMT (C). The signal represents local macrophage accumulation in 4T1 tumors, implanted in the flanks of mice (adopted with permission of [220]). (D–G) Homogeneous tracer distribution in tumors after injection of control IgG-Cy7 (D) and TAM-targeted S100A9-Cy5.5, which accumulates in the tumor periphery (E). The TAM activity reflects the tumor malignancy: S100A9-Cy5.5 gives a stronger signal in highly malignant 4T1 tumors (F) than in slow-growing, less aggressive 67NR tumors (G). Inserts (upper right corner) show corresponding immunohistochemistry of S100A9+ TAMs (adopted with permission of [218]).
See this image and copyright information in PMC

References

    1. Stratton M.R. Exploring the Genomes of Cancer Cells: Progress and Promise. Science. 2011;331:1553–1558. doi: 10.1126/science.1204040. - DOI - PubMed
    1. Marcus A., Gowen B.G., Thompson T.W., Iannello A., Ardolino M., Deng W., Wang L., Shifrin N., Raulet D.H. Chapter Three Recognition of Tumors by the Innate Immune System and Natural Killer Cells. Adv. Immunol. 2014;122:91–128. doi: 10.1016/b978-0-12-800267-4.00003-1. - DOI - PMC - PubMed
    1. Duan Q., Zhang H., Zheng J., Zhang L. Turning Cold into Hot: Firing up the Tumor Microenvironment. Trends Cancer. 2020;6:605–618. doi: 10.1016/j.trecan.2020.02.022. - DOI - PubMed
    1. Nagelkerke A., Bussink J., Rowan A.E., Span P.N. The Mechanical Microenvironment in Cancer: How Physics Affects Tumours. Semin. Cancer Biol. 2015;35:62–70. doi: 10.1016/j.semcancer.2015.09.001. - DOI - PubMed
    1. Ferrao P.T., Behren A., Anderson R.L., Thompson E.W. Editorial: Cellular and Phenotypic Plasticity in Cancer. Front. Oncol. 2015;5:171. doi: 10.3389/fonc.2015.00171. - DOI - PMC - PubMed