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      Active ingredients of traditional Chinese medicine for enhancing the effect of tumor immunotherapy

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          Abstract

          Immunotherapy is a type of treatment that uses our own immune system to fight cancer. Studies have shown that traditional Chinese medicine (TCM) has antitumor activity and can enhance host immunity. This article briefly describes the immunomodulatory and escape mechanisms in tumors, as well as highlights and summarizes the antitumor immunomodulatory activities of some representative active ingredients of TCM. Finally, this article puts forward some opinions on the future research and clinical application of TCM, aiming to promote the clinical applications of TCM in tumor immunotherapy and to provide new ideas for the research of tumor immunotherapy using TCM.

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          Most cited references156

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          Interaction between microbiota and immunity in health and disease

          The interplay between the commensal microbiota and the mammalian immune system development and function includes multifold interactions in homeostasis and disease. The microbiome plays critical roles in the training and development of major components of the host’s innate and adaptive immune system, while the immune system orchestrates the maintenance of key features of host-microbe symbiosis. In a genetically susceptible host, imbalances in microbiota-immunity interactions under defined environmental contexts are believed to contribute to the pathogenesis of a multitude of immune-mediated disorders. Here, we review features of microbiome-immunity crosstalk and their roles in health and disease, while providing examples of molecular mechanisms orchestrating these interactions in the intestine and extra-intestinal organs. We highlight aspects of the current knowledge, challenges and limitations in achieving causal understanding of host immune-microbiome interactions, as well as their impact on immune-mediated diseases, and discuss how these insights may translate towards future development of microbiome-targeted therapeutic interventions.
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            Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

            Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of the tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote tumor growth, angiogenesis, invasion and metastasis, along with extracellular matrix (ECM) remodeling and even chemoresistance. Numerous previous studies have confirmed the critical role of the interaction between CAFs and tumor cells in tumorigenesis and development. However, recently, the mutual effects of CAFs and the tumor immune microenvironment (TIME) have been identified as another key factor in promoting tumor progression. The TIME mainly consists of distinct immune cell populations in tumor islets and is highly associated with the antitumor immunological state in the TME. CAFs interact with tumor-infiltrating immune cells as well as other immune components within the TIME via the secretion of various cytokines, growth factors, chemokines, exosomes and other effector molecules, consequently shaping an immunosuppressive TME that enables cancer cells to evade surveillance of the immune system. In-depth studies of CAFs and immune microenvironment interactions, particularly the complicated mechanisms connecting CAFs with immune cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding the direct and indirect crosstalk between CAFs and infiltrating immune cells and further summarize the possible immunoinhibitory mechanisms induced by CAFs in the TME. In addition, we present current related CAF-targeting immunotherapies and briefly describe some future perspectives on CAF research in the end.
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              Tumor-Associated Macrophages in Tumor Immunity

              Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. The former typically exerts anti-tumor functions, including directly mediate cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; the latter can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis, and lead to tumor progression. Both M1 and M2 macrophages have high degree of plasticity and thus can be converted into each other upon tumor microenvironment changes or therapeutic interventions. As the relationship between TAMs and malignant tumors becoming clearer, TAMs have become a promising target for developing new cancer treatment. In this review, we summarize the origin and types of TAMs, TAMs interaction with tumors and tumor microenvironment, and up-to-date treatment strategies targeting TAMs.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                10 March 2023
                2023
                : 14
                : 1133050
                Affiliations
                [1] 1 National Engineering Research Center for Marine Aquaculture, Institute of Innovation & Application, Zhejiang Ocean University , Zhoushan, Zhejiang, China
                [2] 2 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [3] 3 C-MER Dennis Lam and Partners Eye Center, Hong Kong International Eye Care Group , Hong Kong, China
                [4] 4 Research Center for Preclinical Medicine, Southwest Medical University , Luzhou, China
                [5] 5 Department of Internal Medicine Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China
                Author notes

                Edited by: Wen Tan, Lanzhou University, China

                Reviewed by: Xianfeng Hui, Xinxiang Medical University, China; Huayi Yang, Macau University of Science and Technology, China

                *Correspondence: Chung-Nga Ko, chungngako@ 123456gmail.com ; Kai Wang, wangkai@ 123456swmu.edu.cn ; Haiyong Wang, wanghaiyong6688@ 123456126.com

                †These authors have contributed equally to this work

                This article was submitted to Nutritional Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2023.1133050
                10036358
                36969211
                cbac77c1-17b7-41f7-9a8b-7527b14d16d0
                Copyright © 2023 Yang, Li, Ko, Wang and Wang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 December 2022
                : 28 February 2023
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 156, Pages: 11, Words: 4859
                Funding
                The work was supported by the National Natural Science Foundation of China (82104477, U19A2010 and 81891012), National Interdisciplinary Innovation Team of Traditional Chinese Medicine (ZYYCXTD-D-202209).
                Categories
                Immunology
                Mini Review

                Immunology
                tumor immunity,immunomodulation,traditional chinese medicine,active ingredients,antitumor immunotherapy,natural products

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