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      Lentinan Inhibits Tumor Progression by Immunomodulation in a Mouse Model of Bladder Cancer

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          Abstract

          Background: Lentinan (LNT), an isolated traditional Chinese herbal component, has antitumor potential. In the current study, the intrinsic mechanism of LNT-induced immunity against bladder cancer was explored in a mouse model. Methods: In the mouse model of bladder cancer, we used flow cytometry to detect the LNT caused population changes of T cells, macrophages, MDSC cells, and Treg cells. ELISA was used to evaluate cytokines expression in the supernatant of splenocytes. Results: We found that the administration of LNT increased the proportions of CD3 +CD4 + and CD3 +CD8 + T cell subsets as well as CD11b +F480 + macrophages, whereas it diminished the subpopulations of CD4 +CD25 +Foxp3 + regulatory T cells (Tregs) and Gr-1 +CD11b + myeloid-derived suppressor cells (MDSCs). LNT also upregulated the expression of interferon (IFN)-γ and interleukin (IL)-12, accompanied by a significant reduction in IL-10 and tumor growth factor (TGF)-β ( P < .05). Our research further confirmed the synergy between LNT and gemcitabine (GEM) to activate immunity and inhibit the growth of bladder tumors in mouse model. Conclusions: LNT induced macrophage activation, followed by the enhanced proliferation of CD4 + and CD8 + T cells, and the upregulated expression of IFN-γ and IL-2. Meanwhile, the proportions of MDSCs and Tregs were downregulated, leading to a reduced expression of the anti-inflammatory cytokines IL-10 and TGF-β. The synergy between LNT and GEM provides additional evidence supporting the application of this traditional Chinese herbal component for bladder cancer therapy.

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          Immunogenic cell death in anticancer chemotherapy and its impact on clinical studies

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            Tumor-Associated Macrophages as Target for Antitumor Therapy

            It is well known that the microenvironment of solid tumors is rich in inflammatory cells that influence tumor growth and development. Macrophages, called tumor-associated macrophages (TAMs), are the most abundant immune cell population present in tumor tissue. Several studies have demonstrated that the density of TAMs is associated with a poor prognosis and positively correlates with tumor growth. Several studies have proved that TAMs may activate and protect tumor stem cells, stimulate their proliferation as well as promote angiogenesis and metastasis. Furthermore, TAMs-derived cytokines and other proteins, such as CCL-17, CCL-22, TGF-β, IL-10, arginase 1, and galectin-3, make a significant contribution to immunosuppression. Since TAMs influence various aspects of cancer progression, there are many attempts to use them as a target for immunotherapy. The numerous studies have shown that the primary tumor growth and the number of metastatic sites can be significantly decreased by decreasing the population of macrophages in tumor tissue, for example, by blocking recruitment of monocytes or eliminating TAMs already present in the tumor tissue. Moreover, there are attempts at reprogramming TAMs into proinflammatory M1 macrophages or neutralizing the protumoral products of TAMs. Another approach uses TAMs for anticancer drug delivery into the tumor environment. In this review, we would like to summarize the clinical and preclinical trials that were focused on macrophages as a target for anticancer therapies.
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              Natural products to prevent drug resistance in cancer chemotherapy: a review

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                Author and article information

                Journal
                Integr Cancer Ther
                Integr Cancer Ther
                ICT
                spict
                Integrative Cancer Therapies
                SAGE Publications (Sage CA: Los Angeles, CA )
                1534-7354
                1552-695X
                31 July 2020
                2020
                : 19
                : 1534735420946823
                Affiliations
                [1 ]Shengjing Hospital of China Medical University, Shenyang, China
                [2 ]College of Basic Medical Sciences, China Medical University, Shenyang, China
                [3 ]Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
                Author notes
                [*]Wenyan Zhao, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Email: cmuzwy@ 123456163.com
                Author information
                https://orcid.org/0000-0002-4343-2394
                Article
                10.1177_1534735420946823
                10.1177/1534735420946823
                7401035
                32735179
                69ac6af8-85e1-4ab1-b3fb-b1838443b0f5
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 22 April 2020
                : 4 July 2020
                : 13 July 2020
                Funding
                Funded by: Department of Science and Technology of Liaoning Province, FundRef https://doi.org/10.13039/501100012131;
                Award ID: 201601116
                Funded by: Shenyang Science and Technology Bureau, FundRef https://doi.org/10.13039/501100007765;
                Award ID: 17-231-1-60
                Categories
                Research Article
                Custom metadata
                January-December 2020
                ts1

                lentinan,bladder cancer,immunomodulation,gemcitabine
                lentinan, bladder cancer, immunomodulation, gemcitabine

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