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      Natural products and their derivatives: Promising modulators of tumor immunotherapy

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          Abstract

          A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid‐derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF‐κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.

          Abstract

          This review aims to summarize the integrated research progress of natural products (e.g. curcumin) on the tumor immunotherapy and key intracellular pathways.

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          Most cited references163

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          Cancer immunotherapy: harnessing the immune system to battle cancer.

          The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
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            Coinhibitory Pathways in Immunotherapy for Cancer.

            The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer.
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              IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation

              Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. IL-10 family cytokines exert essential functions to maintain tissue homeostasis during infection and inflammation through restriction of excessive inflammatory responses, upregulation of innate immunity, and promotion of tissue repairing mechanisms. Their important functions in diseases are supported by data from many preclinical models, human genetic studies, and clinical interventions. Despite significant efforts, however, there is still no clinically approved therapy through manipulating IL-10 family cytokines. Here, we summarize the recent progress in understanding the biology of this family of cytokines, suggesting more specific strategies to maneuver these cytokines for the effective treatment of inflammatory diseases and cancers.
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                Author and article information

                Contributors
                chenjiaxu@hotmail.com
                Journal
                J Leukoc Biol
                J. Leukoc. Biol
                10.1002/(ISSN)1938-3673
                JLB
                Journal of Leukocyte Biology
                John Wiley and Sons Inc. (Hoboken )
                0741-5400
                1938-3673
                17 July 2020
                August 2020
                : 108
                : 2 , Targeted Science — Special Focus Issue ( doiID: 10.1002/jlb.v108.2 )
                : 493-508
                Affiliations
                [ 1 ] Formula‐Pattern Research Center School of Traditional Chinese Medicine Jinan University Guangzhou China
                [ 2 ] Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research Jinan University Guangzhou China
                [ 3 ] Department of Pharmacy Shenzhen Hospital of Guangzhou University of Chinese Medicine Shenzhen China
                Author notes
                [*] [* ] Correspondence

                Jia‐Xu Chen, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China

                Email: chenjiaxu@ 123456hotmail.com

                Author information
                https://orcid.org/0000-0002-5570-6233
                Article
                JLB10686
                10.1002/JLB.3MR0320-444R
                7496826
                32678943
                2bb4abf5-18ef-45eb-811d-c10dd0ae0f3e
                © 2020 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 01 December 2019
                : 17 March 2020
                : 06 April 2020
                Page count
                Figures: 3, Tables: 1, Pages: 16, Words: 11834
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81973748
                Award ID: 81630104
                Award ID: 81803790
                Award ID: 81904077
                Funded by: National Natural Science Foundation of Guangdong
                Award ID: 2020A1515011090
                Award ID: 2018A0303130112
                Funded by: Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University
                Award ID: 201911
                Categories
                Review
                5th National Conference of Chinese Medicine and Immunology
                Guest Editors: Chuanjian Lu, Honglin Wang, Runyue Huang, Zhenhua Dai, Xiaojuan He, and Lin Han
                Reviews
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.0 mode:remove_FC converted:11.09.2020

                Hematology
                cardiotonic steroids,polyphenolics,polysaccharides,terpenoids,tregs,tumor immunotherapy
                Hematology
                cardiotonic steroids, polyphenolics, polysaccharides, terpenoids, tregs, tumor immunotherapy

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