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      Tumor-associated macrophages in cancer: recent advancements in cancer nanoimmunotherapies

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          Abstract

          Cancer immunotherapy has emerged as a novel cancer treatment, although recent immunotherapy trials have produced suboptimal outcomes, with durable responses seen only in a small number of patients. The tumor microenvironment (TME) has been shown to be responsible for tumor immune escape and therapy failure. The vital component of the TME is tumor-associated macrophages (TAMs), which are usually associated with poor prognosis and drug resistance, including immunotherapies, and have emerged as promising targets for cancer immunotherapy. Recently, nanoparticles, because of their unique physicochemical characteristics, have emerged as crucial translational moieties in tackling tumor-promoting TAMs that amplify immune responses and sensitize tumors to immunotherapies in a safe and effective manner. In this review, we mainly described the current potential nanomaterial-based therapeutic strategies that target TAMs, including restricting TAMs survival, inhibiting TAMs recruitment to tumors and functionally repolarizing tumor-supportive TAMs to antitumor type. The current understanding of the origin and polarization of TAMs, their crucial role in cancer progression and prognostic significance was also discussed in this review. We also highlighted the recent evolution of chimeric antigen receptor (CAR)-macrophage cell therapy.

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          Cancer immunotherapy using checkpoint blockade

          The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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            Engineering precision nanoparticles for drug delivery

            In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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              Tumour-associated macrophages as treatment targets in oncology

              Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
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                Author and article information

                Contributors
                verocay@snuh.org
                Journal
                J Exp Clin Cancer Res
                J Exp Clin Cancer Res
                Journal of Experimental & Clinical Cancer Research : CR
                BioMed Central (London )
                0392-9078
                1756-9966
                19 February 2022
                19 February 2022
                2022
                : 41
                : 68
                Affiliations
                [1 ]GRID grid.412484.f, ISNI 0000 0001 0302 820X, Department of Radiology, , Seoul National University Hospital, Seoul National University College of Medicine, ; 101, Daehak-ro, Jongno-gu, Seoul, 03080 South Korea
                [2 ]GRID grid.410720.0, ISNI 0000 0004 1784 4496, Center for Nanoparticle Research, Institute for Basic Science (IBS), ; Seoul, 00826 Republic of Korea
                [3 ]GRID grid.31501.36, ISNI 0000 0004 0470 5905, School of Chemical and Biological Engineering, Seoul National University, ; Seoul, 00826 Republic of Korea
                Author information
                http://orcid.org/0000-0002-0412-2270
                Article
                2272
                10.1186/s13046-022-02272-x
                8857848
                35183252
                565083e2-74b6-43b1-bb10-4f2164d2132a
                © 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
                : 26 November 2021
                : 22 January 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003625, Ministry of Health and Welfare;
                Award ID: HI16C1111
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003621, Ministry of Science, ICT and Future Planning;
                Award ID: NRF-2016M3C7A1914002
                Award ID: NRF-2020R1A2C2008949
                Award ID: NRF-2020R1A4A1018714
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002551, Seoul National University;
                Award ID: IBS-R006-A1
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2022

                Oncology & Radiotherapy
                tumor-associated macrophages,tumor microenvironment,carcinogenesis,macrophage repolarization,nanomaterials,nanoimmunotherapies

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