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      Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

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          Abstract

          Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

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          Oncology meets immunology: the cancer-immunity cycle.

          The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Analysis of nanoparticle delivery to tumours

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              The Tumor Microenvironment Innately Modulates Cancer Progression

              Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and NK cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Crosstalk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
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                Author and article information

                Contributors
                phcgs@nus.edu.sg
                yuanzhennan123@hrbmu.edu.cn
                leospiv@hrbmu.edu.cn
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                2 April 2024
                2 April 2024
                2024
                : 17
                : 16
                Affiliations
                [1 ]GRID grid.460007.5, ISNI 0000 0004 1791 6584, Department of Thoracic Surgery, , Tangdu Hospital, Air Force Medical University, ; 569 Xinsi Road, Xi’an, 710038 China
                [2 ]Department of Rehabilitation Medicine, Chongqing Public Health Medical Center, ( https://ror.org/04dcmpg83) Chongqing, China
                [3 ]Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, ( https://ror.org/01f77gp95) Harbin, China
                [4 ]Department of General Surgery, Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, ( https://ror.org/01vy4gh70) Shenzhen, 518055 Guangdong China
                [5 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, , Fudan University, ; Shanghai, 200032 China
                [6 ]GRID grid.440144.1, ISNI 0000 0004 1803 8437, Department of Radiation Oncology, , Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, ; Jinan, 250000 Shandong China
                [7 ]Xsphera Biosciences, Translational Medicine Group, ( https://ror.org/0519z1231) 6 Tide Street, Boston, MA 02210 USA
                [8 ]GRID grid.38142.3c, ISNI 000000041936754X, Department of Medical Oncology, , Dana-Farber Cancer Institute, Harvard Medical School, ; Boston, MA 02115 USA
                [9 ]Blood Cell Development and Function Program, Fox Chase Cancer Center, ( https://ror.org/0567t7073) Philadelphia, PA USA
                [10 ]School of Public Health, Benedictine University, ( https://ror.org/053fh2363) Lisle, USA
                [11 ]Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, ( https://ror.org/03rmrcq20) Vancouver, BC V6H3Z6 Canada
                [12 ]Cumming School of Medicine, Arnie Charbonneau Cancer Research Institute, University of Calgary, ( https://ror.org/03yjb2x39) Calgary, AB T2N 4Z6 Canada
                [13 ]Department of Medical Sciences, University of Calgary, ( https://ror.org/03yjb2x39) Calgary, AB T2N 4Z6 Canada
                [14 ]GRID grid.4280.e, ISNI 0000 0001 2180 6431, Present Address: NUS Center for Cancer Research (N2CR), , Yong Loo Lin School of Medicine, National University of Singapore, ; Singapore, 117599 Singapore
                [15 ]Present Address: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, ( https://ror.org/01tgyzw49) 16 Medical Drive, Singapore, 117600 Singapore
                [16 ]Laboratory of NF-κB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), ( https://ror.org/04xpsrn94) 61 Biopolis Drive, Proteos, 138673 Singapore, Republic of Singapore
                [17 ]The Graduate School, Augusta University, ( https://ror.org/012mef835) 30912 Augusta, GA USA
                [18 ]Department of Oncology Surgery, Harbin Medical University Cancer Hospital, ( https://ror.org/01f77gp95) Harbin, China
                [19 ]Key Laboratory of Tumor Immunology in Heilongjiang, Harbin, China
                Article
                1535
                10.1186/s13045-024-01535-8
                10986145
                38566199
                db178e62-1cbc-4a9a-8fb5-53f457b7c275
                © The Author(s) 2024

                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/. 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
                : 30 December 2023
                : 15 March 2024
                Categories
                Review
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Oncology & Radiotherapy
                bioengineered nanostructures; cancer immunotherapy,immune evasion nanoparticles,tumor microenvironment

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