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      Roles of macrophages in tumor development: a spatiotemporal perspective

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          Abstract

          Macrophages are critical regulators of tissue homeostasis but are also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support tumor development. While we know that TAMs are the dominant immune cells in the TME, their vast heterogeneity and associated functions are only just being unraveled. In this review, we outline the various known TAM populations found thus far and delineate their specialized roles associated with the main stages of cancer progression. We discuss how macrophages may prime the premetastatic niche to enable the growth of a metastasis and then how subsequent metastasis-associated macrophages can support secondary tumor growth. Finally, we speculate on the challenges that remain to be overcome in TAM research.

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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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            Understanding the tumor immune microenvironment (TIME) for effective therapy

            The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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              Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication

              The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ill-defined. Here, we discuss the current knowledge on the specificities of exosomes and other types of extracellular vesicles, and their roles as important agents of cell-to-cell communication.
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                Author and article information

                Contributors
                florent.ginhoux@gustaveroussy.fr
                camille.bleriot@cnrs.fr
                Journal
                Cell Mol Immunol
                Cell Mol Immunol
                Cellular and Molecular Immunology
                Nature Publishing Group UK (London )
                1672-7681
                2042-0226
                10 July 2023
                10 July 2023
                September 2023
                : 20
                : 9
                : 983-992
                Affiliations
                [1 ]GRID grid.14925.3b, ISNI 0000 0001 2284 9388, Institut Gustave Roussy, INSERM U1015, ; Villejuif, France
                [2 ]GRID grid.185448.4, ISNI 0000 0004 0637 0221, Singapore Immunology Network (SIgN), Agency for Science, , Technology and Research (A∗STAR), ; Singapore, Singapore
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Shanghai Institute of Immunology, , Shanghai JiaoTong University School of Medicine, ; Shanghai, China
                [4 ]GRID grid.512024.0, ISNI 0000 0004 8513 1236, Translational Immunology Institute, , SingHealth Duke-NUS, ; Singapore, Singapore
                [5 ]GRID grid.508487.6, ISNI 0000 0004 7885 7602, Institut Necker des Enfants Malades, INSERM, CNRS, , Université Paris Cité, ; Paris, France
                Author information
                http://orcid.org/0000-0002-2857-7755
                Article
                1061
                10.1038/s41423-023-01061-6
                10468537
                37429944
                5e8a5cd7-3301-4e43-8b44-b19ffde671a8
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 April 2023
                : 16 June 2023
                Categories
                Review Article
                Custom metadata
                © CSI and USTC 2023

                Immunology
                macrophages,tumor associated macrophages,tumor microenvironment,metastasis,phagocytes,immunosurveillance

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