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      Targeting macrophages: a novel treatment strategy in solid tumors

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          Abstract

          In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

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          Most cited references212

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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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            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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              Inflammation and Cancer: Triggers, Mechanisms, and Consequences

              Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression and metastasis. We discuss how tumor promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis or tissue repair, and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatio-temporal considerations. Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for the further development of anti-cancer therapies. Grivennikov and Greten review the mechanisms underlying the initiation of pro-tumorigenic inflammatory responses, how these evolve throughout the different stages of tumor development and the plasticity of the cells within the tumor microenvironment.
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                Author and article information

                Contributors
                zlyylw3028@zzu.edu.cn
                zlyyxulinping1475@zzu.edu.cn
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                12 December 2022
                12 December 2022
                2022
                : 20
                : 586
                Affiliations
                [1 ]GRID grid.414008.9, ISNI 0000 0004 1799 4638, Department of Research and Foreign Affairs, , The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, ; Zhengzhou, 450008 China
                [2 ]GRID grid.412633.1, ISNI 0000 0004 1799 0733, Department of Hematology, , The First Affiliated Hospital of Zhengzhou University, ; Zhengzhou, 450052 Henan China
                [3 ]GRID grid.207374.5, ISNI 0000 0001 2189 3846, Academy of Medical Sciences of Zhengzhou University, ; Zhengzhou, 450052 China
                [4 ]GRID grid.414008.9, ISNI 0000 0004 1799 4638, Department of Hematology, , The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, ; Zhengzhou, 450008 China
                Author information
                http://orcid.org/0000-0001-5550-508X
                Article
                3813
                10.1186/s12967-022-03813-w
                9743606
                36510315
                3cb6e2ec-0861-43ce-8a7b-040b67c6fe98
                © The Author(s) 2022

                Open AccessThis 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/. 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 in a credit line to the data.

                History
                : 28 August 2022
                : 6 December 2022
                Funding
                Funded by: Natural Science Foundation of China
                Award ID: 82270149
                Award Recipient :
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2022T150592
                Award ID: 2021M692930
                Award Recipient :
                Funded by: Key Research Projects of Henan Higher Education Institutions
                Award ID: 21A320049
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100017700, Henan Provincial Science and Technology Research Project;
                Award ID: SBGJ202102063
                Award ID: LHGJ20220305
                Award ID: SBGJ202101007
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Medicine
                tumor-associated macrophages,solid tumors,immunotherapeutic strategies,cd47 mab,cd47 based bsab,car-m

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