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      Tumor-associated macrophages: an accomplice in solid tumor progression

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          Abstract

          In many solid tumor types, tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME). Moreover, TAMs infiltration is strongly associated with poor survival in solid tumor patients. In this review, we describe the origins of TAMs and their polarization state dictated by the TME. We also specifically focus on the role of TAMs in promoting tumor growth, enhancing cancer cells resistance to chemotherapy and radiotherapy, promoting tumor angiogenesis, inducing tumor migration and invasion and metastasis, activating immunosuppression. In addition, we discuss TAMs can be used as therapeutic targets of solid tumor in clinics. The therapeutic strategies include clearing macrophages and inhibiting the activation of TAMs, promoting macrophage phagocytic activity, limiting monocyte recruitment and other targeted TAMs therapies.

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          Most cited references108

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          Microenvironmental regulation of tumor progression and metastasis.

          Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
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            Tumour-associated macrophages as treatment targets in oncology

            Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
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              Macrophage plasticity and polarization: in vivo veritas.

              Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
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                Author and article information

                Contributors
                +86-371-66913236 , chenyibing@zzu.edu.cn
                +86-20-85211436 , zouzhengzhi@m.scnu.edu.cn
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                20 October 2019
                20 October 2019
                2019
                : 26
                : 78
                Affiliations
                [1 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital, , Zhengzhou University, ; 1 Jianshe Road East, Zhengzhou, 450052 Henan China
                [2 ]ISNI 0000 0001 2189 3846, GRID grid.207374.5, Department of Neurosurgery, First Affiliated Hospital, , Zhengzhou University, ; Zhengzhou, 450052 China
                [3 ]ISNI 0000 0004 0368 7397, GRID grid.263785.d, MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, , South China Normal University, ; Guangzhou, 510631 Guangdong China
                Article
                568
                10.1186/s12929-019-0568-z
                6800990
                31629410
                0faea4a8-2187-469c-ae85-0257cdd32b6e
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 June 2019
                : 16 September 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81772643
                Award ID: 81772803
                Award ID: 81402281
                Award ID: 81402187
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2019

                Molecular medicine
                tumor-associated macrophages,solid tumor,tumor growth,chemotherapy and radiotherapy resistance,angiogenesis,migration,invasion,metastasis,immunosuppression,therapeutic target

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