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      Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products Translated title: Traitement des hépatomes murins avec des cellules dendritiques mûres stimulées par des produits d’excrétion-sécrétion de Trichinella spiralis

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          Abstract

          Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group ( p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

          Translated abstract

          Les produits d’excrétion-sécrétion (PES) du nématode Trichinella spiralis contiennent des substances actives antitumorales qui inhibent la croissance tumorale. Les cellules dendritiques (CD) mûres jouent un rôle essentiel dans l’immunité anti-tumorale de l’organisme. En tant que produits dérivés d’agents pathogènes, il convient de déterminer si les PES de T. spiralis réduisent l’effet antitumoral des CD mûrs de l’hôte, avant leur application aux tumeurs des patients. Par conséquent, l’objectif de ce travail était d’évaluer l’effet immunologique des CD stimulées par les PES de T. spiralis chez des souris porteuses de tumeurs H22. Les souris modèles à tumeurs H22 dans cette étude ont été réparties au hasard en quatre groupes selon le traitement : groupe témoin PBS, groupe PES, groupe CD et groupe CD stimulés par les PES de T. spiralis (CD+PES). L’effet antitumoral a été évalué par le taux d’inhibition des tumeurs et la détection des cytokines en utilisant un dosage ELISA. Les résultats ont montré une inhibition significative de la croissance tumorale dans les groupes CD+PES, CD et PES par rapport au groupe témoin PBS ( p < 0,01, p < 0,01 et p < 0,05, respectivement). Cependant, aucune différence significative n’a été observée sur le taux d’inhibition de la tumeur entre les groupes CD+PES et CD. La diminution de l’IL-4, de l’IL-6, de l’IL-10 et l’augmentation de l’IFN-γ entre les groupes CD et CD+PES n’étaient pas non plus significatives. Ainsi, les CD stimulées par les PES n’ont pas réduit l’effet antitumoral des CD mûrs, ce qui a démontré que les PES de T. spiralis n’affectaient pas l’effet antitumoral des CD mûrs en modulant la réponse immunitaire de l’hôte et que les PES sont sûrs en immunologie antitumorale quand ils sont appliqués à des souris modèles tumorales.

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          Most cited references45

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          Dendritic Cells and Cancer Immunity.

          Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors. Bypassing suppressive pathways or directly activating DCs can unleash a T-cell response, and although clinical efficacy has proven elusive, therapeutic targeting of DCs continues to hold translational potential in combinatorial approaches.
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            Induction of Interleukin-10 Producing Dendritic Cells As a Tool to Suppress Allergen-Specific T Helper 2 Responses

            Dendritic cells (DCs) are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10) is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage. Because of their important role in preventing autoimmune diseases, transplant rejection, allergic reactions, or in controlling chronic inflammation DCs have become an interesting tool to modulate antigen-specific immune responses. For the treatment of allergic inflammation, the aim is to downregulate allergen-specific T helper 2 (Th2) responses and the associated clinical symptoms [allergen-driven Th2 activation, Th2-driven immunoglobulin E (IgE) production, IgE-mediated mast cell and basophil activation, allergic inflammation]. Here, combining the presentation of allergens by DCs with a pro-tolerogenic, IL-10-producing phenotype is of special interest to modulate allergen-specific immune responses in the treatment of allergic diseases. This review discusses the reported strategies to induce DC-derived IL-10 secretion for the suppression of allergen-specific Th2-responses with a focus on IL-10 treatment, IL-10 transduction, and the usage of both whole bacteria and bacteria-derived components. Interestingly, while IL-10-producing DCs induced either by IL-10 treatment or IL-10 transduction are arrested in an immature/semi-mature state, treatment of DCs with live or killed bacteria as well as isolated bacterial components results in the induction of both anti-inflammatory IL-10 and pro-inflammatory, Th1-promoting IL-12 secretion often paralleled by an enhanced expression of co-stimulatory molecules on the stimulated DCs. By the secretion of DC-derived exosomes or CC-chemokine ligand 18, as well as the expression of inhibitory molecules like cytotoxic T lymphocyte-associated antigen 4, TNF receptor superfamily member 4, Ig-like transcript-22/cluster of differentiation 85, or programmed death-1, IL-10-producing DCs have been repeatedly shown to suppress antigen-specific Th2-responses. Therefore, DC-based vaccination approaches hold great potential to improve the treatment of allergic diseases.
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              Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients

              A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP+ DCs is robustly associated with an immune contexture characterized by TH1 polarization and cytotoxic activity. We showed that both mature DCs and CD20+ B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP+ DCs and CD20+ B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP+ DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity. Electronic supplementary material The online version of this article (10.1186/s40425-018-0446-3) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2020
                21 July 2020
                : 27
                : ( publisher-idID: parasite/2020/01 )
                : 47
                Affiliations
                [1 ] Key Laboratory for Zoonoses Research, Ministry of Education, Institute of Zoonoses, College of Veterinary Medicine, Jilin University, OIE Collaborating Center on Foodborne Parasites in Asian-Pacific Region Changchun 130062 P.R. China
                Author notes
                [* ]Corresponding author: xuelin@ 123456jlu.edu.cn
                Author information
                http://orcid.org/0000-0001-9892-1657
                http://orcid.org/0000-0001-7303-8534
                Article
                parasite200003 10.1051/parasite/2020045
                10.1051/parasite/2020045
                7373160
                32692308
                fe892dcd-a50f-43ed-8f8d-4eae27c64bf9
                © J. Ding et al., published by EDP Sciences, 2020

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 December 2019
                : 03 July 2020
                Page count
                Figures: 4, Tables: 1, Equations: 1, References: 48, Pages: 8
                Categories
                Research Article

                trichinella spiralis,excretory/secretory products,dendritic cells,h22

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