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      Role of chemokine systems in cancer and inflammatory diseases

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          Abstract

          Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

          Abstract

          Chemokines are a large family of small secreted proteins that coordinate and recruit immune cells into and out of tissues and to participate in regulating the interactions between immune cells. The chemokine/chemokine receptor axis is involved in the progression of multiple malignancy types and almost all inflammatory diseases. This review summarizes recent advances of chemokine system in antitumor and protumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases.

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          Most cited references413

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          Inflammatory responses and inflammation-associated diseases in organs

          Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.
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            Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy

            This Review details how chemokines shape immune responses in the tumour microenvironment through their effects on immune cells, stromal cells and the tumour cells themselves. The authors discuss the potential of targeting chemokine networks for cancer therapy.
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              CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation - A target for novel cancer therapy.

              Chemokines are proteins which induce chemotaxis, promote differentiation of immune cells, and cause tissue extravasation. Given these properties, their role in anti-tumor immune response in the cancer environment is of great interest. Although immunotherapy has shown clinical benefit for some cancer patients, other patients do not respond. One of the mechanisms of resistance to checkpoint inhibitors may be chemokine signaling. The CXCL9, -10, -11/CXCR3 axis regulates immune cell migration, differentiation, and activation, leading to tumor suppression (paracrine axis). However, there are some reports that show involvements of this axis in tumor growth and metastasis (autocrine axis). Thus, a better understanding of CXCL9, -10, -11/CXCR3 axis is necessary to develop effective cancer control. In this article, we summarize recent evidence regarding CXCL9, CXCL10, CXCL11/CXCR3 axis in the immune system and discuss their potential role in cancer treatment.
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                Author and article information

                Contributors
                min.wu@und.edu
                xiazhaoscu@126.com
                Journal
                MedComm (2020)
                MedComm (2020)
                10.1002/(ISSN)2688-2663
                MCO2
                MedComm
                John Wiley and Sons Inc. (Hoboken )
                2688-2663
                08 June 2022
                June 2022
                : 3
                : 2 ( doiID: 10.1002/mco2.v3.2 )
                : e147
                Affiliations
                [ 1 ] Department of Gynecology and Obstetrics, Development and Related Disease of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education West China Second Hospital Sichuan University Chengdu China
                [ 2 ] Department of Biomedical Sciences, School of Medicine and Health Sciences University of North Dakota Grand Forks North Dakota USA
                Author notes
                [*] [* ] Correspondence

                Min Wu, Grand Forks, North Dakota 58203, USA.

                Email: min.wu@ 123456und.edu

                Xia Zhao, 20 South Renmin Road, Block 3, Chengdu 610041, China.

                Email: xiazhaoscu@ 123456126.com

                Article
                MCO2147
                10.1002/mco2.147
                9175564
                35702353
                e168241f-49b7-4889-a408-5f9be1835b15
                © 2022 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2022
                : 21 March 2022
                : 11 May 2022
                Page count
                Figures: 5, Tables: 2, Pages: 41, Words: 24221
                Funding
                Funded by: National Major Scientific and Technological Special Project for the “Significant New Drugs Development”
                Award ID: 2018ZX09201018‐013
                Funded by: National Science and Technology Major Projects for Major New Drugs Innovation and Development
                Award ID: 2018ZX09733001‐004
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                June 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.6 mode:remove_FC converted:08.06.2022

                cancer progression,chemokine,chemokine receptor,inflammatory diseases,tumor microenvironment (tme)

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