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Cancers 2014, 6(3), 1670-1690; doi:10.3390/cancers6031670

Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

1
Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
2
Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
3
Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
4
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan
*
Author to whom correspondence should be addressed.
Received: 26 May 2014 / Revised: 27 July 2014 / Accepted: 5 August 2014 / Published: 13 August 2014
(This article belongs to the Special Issue Tumor Associated Macrophages)
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Abstract

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy. View Full-Text
Keywords: tumor-associated macrophage; M2 macrophage; tumor progression; angiogenesis; tumor metastasis; immunosuppression; cancer stem cells tumor-associated macrophage; M2 macrophage; tumor progression; angiogenesis; tumor metastasis; immunosuppression; cancer stem cells
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Chanmee, T.; Ontong, P.; Konno, K.; Itano, N. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment. Cancers 2014, 6, 1670-1690.

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