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Finally, phagocytosis is a general property of macrophages, but not a reliable predictor of M1/inhibit- or M2/heal-type responses. 8, 958969 (2008). 36, 53 (2017). Calcitonin receptor antibodies in the identification of osteoclasts. Science 344, 921925 (2014). 32, 123145 (2011). Nakamura, K. et al. Drug Deliv. Sci. Trends Immunol. Mills, C. D. Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue. J. Clin. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. J. Innate Immun. Trends Immunol. Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-beta signaling pathway. Although most of these strategies are not meant to target macrophages directly or originally, macrophages contribute significantly to the final outcomes. Sun, D. et al. Origin of monocytes and macrophages in a committed progenitor. Nguyen, K. D. et al. 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This notion was further confirmed by RNA velocity and phylogenetic trees of macrophages from various tissues. 14, 603622 (2015). Gautier, E. L. et al. Giavridis, T. et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. In contrast, not all cancer cells express just one specific antigen because of tumor heterogeneity. Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Anat. Hulsmans, M. et al. Immunity 38, 792804 (2013). Rev. Cancer Immunol. Hamieh, M. et al. Google Scholar. (4) Removal of the macrophage blockade;207,212,213 interactions between CD47 on tumors and SIRP on macrophages help tumor cells evade macrophage phagocytosis. 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Ornithine, VEGF, EGF, and TGF- are examples of tumor-promoting factors derived from macrophages, while nitric oxide generated by inducible nitric oxide synthase in macrophages can inhibit tumor growth.32,33,65,66 Macrophages have been demonstrated to be involved directly or indirectly in several key features of malignant tumors, including angiogenesis, invasiveness, metastasis, regulation of the tumor microenvironment, and therapeutic resistance (Fig. Blood 133, 697709 (2019). To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer. Nat. Fortunately, the polarization of macrophages can be repolarized. Nat. 12, 626632 (2019). Dal-Secco, D. et al. J. Hematol. Blood 107, 21122122 (2006). Cancer Res. J. Innate Immun. Du Cheyne, C., Tay, H. & De Spiegelaere, W. 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The transformation from M2- to M1-phenotype macrophages is sufficient to cause a tumor-suppressive effect.194,195,196 Of note, the polarization of macrophages is independent of T cells, while M1 macrophages are able to induce Th1 immune responses, and M2 macrophages can trigger Th2 immune responses.197 This provides an opportunity to target macrophages in cancer immunotherapy. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. demonstrated that cooperation between T cells and macrophages is required to achieve the effects of a therapeutic vaccine. Nat. Activated HIF1alpha of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer. Targeting tumor-associated macrophages in cancer. Mills, C. D. M1 and M2 macrophages: oracles of health and disease. Odegaard, J. I. et al. Article Zhu, X. et al. Because macrophages can be differentiated to M1- or M2-type cells with either GM-CSF or M-CSF, respectively, and can be classically activated by proinflammatory stimuli (IFN-gamma/LPS) or undergo alternative activation with cytokines such as IL-4 or IL-10, we have analyzed the effect of these different polarization programs on the phagocytosis m. Clin. Oncol. 79, 146158 (2019). Mantovani, A., Sozzani, S., Locati, M., Allavena, P. & Sica, A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Mason, S. D. & Joyce, J. Macrophages present these peptides to MHC class II molecules on their surface and stimulate T-cell proliferation and activation with the synergistic effect of costimulatory molecules.55,56 It has been reported that adult macrophages are primarily responsible for host defense, while fetal macrophages are involved in tissue remodeling.40 Macrophages play an important role in the development and homeostasis. Sci. 138, 550565 (1987). Whether the function of macrophages leads to sensitization or resistance to traditional therapy is complex.128,129 Better understanding of the mechanisms can improve the efficacy of traditional oncotherapy. J. Immunother. Due to the limitations and shortages of traditional cancer treatments, immunotherapy has become the most promising cancer treatment. Macrophages facilitate electrical conduction in the heart. Immunol. Morgan, R. A. et al. The conflicting conclusions might be due to the use of different cell ratios, culture times and means, and polarization methods for macrophages. Qian, B. Gray, E. E. & Cyster, J. G. Lymph node macrophages. Salmaninejad, A. et al. Wu, Y. Rahal, O. M. et al. & Riechelmann, H. Epithelial to mesenchymal transition: a mechanism that fuels cancer radio/chemoresistance. Arlauckas, S. P. et al. Crit. Med. Circ. DeNardo, D. G. & Ruffell, B. Macrophages as regulators of tumour immunity and immunotherapy. Noguchi, T. et al. 19, 14231437 (2013). Macrophages (Ms) are critical to the innate immune response to S. aureus and commence their antimicrobial activity after internalizing the pathogen (9, 10).However, this immune defense mechanism is not commonly activated in the presence of postoperative infections, which allows infections to persist ().Furthermore, the implant itself triggers a local tissue response, leading to a niche of . Neurosci. Nat. As reported, the incidence of cancerogenesis is low in invertebrates with no T or B cells, indicating that innate immune cells are of great importance for preventing the initiation and development of cancer.189,190,191 In addition to their supporting role in all kinds of immunotherapies, macrophages may become a promising target in future cancer immunotherapy.33,192 Many targets and pharmacological agents related to macrophages in oncotherapy have been summarized in recent reviews.128,193 We updated the typical macrophages-targeting agents that have been registered for cancer-related clinical trials (excluding projects those are in the status of terminated, withdrawn, unknown, not yet recruiting) in Table2.
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