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      Targeting macrophages in cancer immunotherapy

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          Abstract

          Immunotherapy is regarded as the most promising treatment for cancers. Various cancer immunotherapies, including adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small-molecule inhibitors, have achieved certain successes. In this review, we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages. To better understand and make better use of this type of cell, their development and differentiation characteristics, categories, typical markers, and functions were collated at the beginning of the review. Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

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          Microenvironmental regulation of tumor progression and metastasis.

          Daniela F Quail, Johanna A Joyce (2013)
          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.
          Article 0 comments Cited 2084 times – based on 0 reviews     Review now
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            Macrophage plasticity, polarization, and function in health and disease.

            Fatemeh Mardani, Abbas Shapouri-Moghaddam, Saeed Mohammadian … (2018)
            Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1β, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.
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              Exploring the full spectrum of macrophage activation.

              David Mosser, Justin Edwards (2008)
              Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
              Article 0 comments Cited 1411 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yunping Luo: ypluo@ibms.pumc.edu.cn
                Journal
                Journal ID (nlm-ta): Signal Transduct Target Ther
                Journal ID (iso-abbrev): Signal Transduct Target Ther
                Title: Signal Transduction and Targeted Therapy
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 2095-9907
                ISSN (Electronic): 2059-3635
                Publication date (Electronic): 26 March 2021
                Publication date PMC-release: 26 March 2021
                Publication date Collection: 2021
                Volume: 6
                Electronic Location Identifier: 127
                Affiliations
                [1 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, , Peking Union Medical College, ; Beijing, China
                [2 ]GRID grid.506261.6, ISNI 0000 0001 0706 7839, Collaborative Innovation Center for Biotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, , Peking Union Medical College, ; Beijing, China
                Article
                Publisher ID: 506
                DOI: 10.1038/s41392-021-00506-6
                PMC ID: 7994399
                PubMed ID: 33767177
                SO-VID: 9654b10f-d059-4436-8292-83bb2df213e4
                Copyright © © The Author(s) 2021
                License:

                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 13 August 2020
                Date revision received : 14 January 2021
                Date accepted : 22 January 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81672914
                Award ID: 81472654
                Award ID: 81601374
                Award Recipient :
                Funded by: the Fundamental Research Funds for the Central Universities (3332020033)
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                Keywords: tumour immunology,drug development
                Data availability:
                Keywords: tumour immunology, drug development

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