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      New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

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          Abstract

          The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

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          Most cited references143

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Immunity, inflammation, and cancer.

            Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. 2010 Elsevier Inc. All rights reserved.
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              Inflammation and cancer.

              Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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                Author and article information

                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi Publishing Corporation
                2314-8861
                2314-7156
                2016
                16 November 2016
                : 2016
                : 9720912
                Affiliations
                1Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medicine Sciences, No. 5 Beixiange, Xicheng District, Beijing 100053, China
                2Beijing University of Chinese Medicine, No. 11 North Third Ring Road East, Chaoyang District, Beijing 100029, China
                3Department of Oncology, Xiyuan Hospital, China Academy of Chinese Medicine Sciences, No. 1 Playground Road, Haidian District, Beijing 100091, China
                4Institute of Basic Research in Clinical Medicine (IBRCM), China Academy of Chinese Medicine Sciences, No. 16 Dongzhimen Nanxiaojie, Dongcheng District, Beijing 100700, China
                Author notes

                Academic Editor: Eyad Elkord

                Author information
                http://orcid.org/0000-0001-6600-9540
                http://orcid.org/0000-0003-0909-4499
                http://orcid.org/0000-0002-3997-6604
                http://orcid.org/0000-0002-2262-5525
                http://orcid.org/0000-0002-6052-2084
                http://orcid.org/0000-0003-1866-8212
                http://orcid.org/0000-0002-0494-9008
                http://orcid.org/0000-0002-6927-7492
                http://orcid.org/0000-0002-1265-0356
                http://orcid.org/0000-0002-6940-9555
                Article
                10.1155/2016/9720912
                5128713
                27975071
                0fcf6664-8a46-46d9-8c25-45e3c2f6306b
                Copyright © 2016 Qiujun Guo et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 June 2016
                : 26 September 2016
                Funding
                Funded by: National Twelfth Five-Year Plan for Science and Technology Support Program of China
                Award ID: 2014BAI10B01
                Funded by: National Natural Science Foundation of China
                Award ID: 81202656
                Award ID: 81273718
                Award ID: 81403346
                Award ID: 81603610
                Categories
                Review Article

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