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Caracterização do infiltrado celular, avaliação dos marcadores de densidade microvascular, (CD31, CD105) e marcador de proliferação celular (Ki-67) no câncer de mama 4T1 em camundongos tratados com vacina de células dendríticas, terapia com Interferon-alpha e trapia combinadaCâncer de mama.Proliferação celular.Angiogênese patológica.Imunoterapia.Células dendríticas.Immunotherapy.Breast cancer.Dendritic cells.Tumor.Cell proliferation.Angiogenesis.Imunologia CelularEste estudo teve como objetivo investigar a influência do tratamento com a vacina de células dendríticas, Interferon-α e terapia combinada (células dendríticas e Interferon-α) na resposta imune no modelo experimental de câncer de mama induzido através da linhagem tumoral 41T. Nessa perspectiva, este estudo analisou células imunes encontradas no baço CD3+, CD4+ e macrófagos CD14+ alterações na síntese das citocinas IL-10, IL-12, IFN-γ, TNF-α e CD25 +, bem como o infiltrado de linfócitos CD3+, CD4+ CD8+ microdensidade vascular (CD31), (CD105) e proliferação celular (Ki-67) no tumor em camundongos Balb / c, inoculados com (4T1). Os animais foram divididos em seis grupos, cada qual com 10 animais: grupo (1) controle (C), grupo sem tratamento e sem tumor, grupo (2) controle dendríticas (DCs), animais tratados com vacina de células dendríticas sem inoculação da linhagem tumoral 4T1, grupo (3) grupo tumor (T), animais inoculados com linhagem tumoral 4T1 e posteriormente tratados com solução salina a 0,9%, grupo (4), grupo tumor dendríticas tratado (T + DCs), animais inoculados com linhagem tumoral 4T1 e subsequentemente tratados com células dendríticas, grupo (5), grupo tratado com IFN-α (T + IFN-α), animais com inoculação de linhagem tumoral 4T1 e subsequentemente tratados IFN-α, e grupo (6), grupo tumor tratado com IFN-α e vacina de células dendríticas (T + IFN-α + DCs), animais inoculados com linhagem tumoral 4T1 e posteriormente tratados com IFN-α e DCs vacina. Observamos que a indução de tumor, nos grupos de imunoterapia combinados com Interferon-α + células dendríticas e imunoterapia isolada somente com Interferon-α, reduziu as quantidades de linfócitos, de linfócitos produtores de citocinas Th1, macrófagos peritoneais e aumentou a presença de citocinas Th2 e células Treg. Os resultados também evidenciaram que as células dendríticas, mesmo na presença do tumor, grupo tumoral (T + DCs), foram capazes de promover uma diminuição na expressão das proteínas envolvidas na microdensidade vascular (CD31), (CD105) e na proliferação celular (Ki-67). Houve também um aumento na expressão de linfócitos CD4+ e CD8+ intratumorais no grupo tratado com vacina de células dendríticas na presença do tumor. Portanto, podemos concluir que o microambiente tumoral parece ter uma forte influência negativa sobre a ação efetora do Interferon-α. Apenas a presença das células dendríticas no tumor promoveu a polarização do sistema Imune para um perfil de padrão de resposta anti-tumoral Th1. No entanto, mais estudos são necessários para buscar o melhor entendimento da biologia e ação adjuvante do IFN-α juntamente com as células dendríticas.This study aims investigate the influence the treatment with dendritic cell vaccine, Interferon- α and combination therapy (dendritic cells and Interferon-α) on the immune response in the proposed experimental model of breast cancer. In this perspective, this study analyzed through assessments of immune cells found in the spleen CD3+ and CD4+ and macrophages CD14+ and changes in the synthesis of cytokines IL-10, IL-12, IFN-γ, TNF-α, and CD25+ as well as the infiltrate of the lymphocyte CD3+, CD4+, CD8+ and vascular microdensity (CD31), (CD105) , cell proliferation (Ki-67), in Balb/c mice, inoculated with (4T1). For this study, we used animals were divided into six groups; the group I, control (C) no treat and no tumor (n=10) animals, group II, control treated with DCs vaccine (DC) (n = 10) animals without inoculation of the 4T1 tumoral lineage and later treated with DCs, group III, tumor (T) (n = 10) animals inoculated with 4T1 tumoral lineage and subsequently treated with 0.9% saline solution, group IV, tumor treated with DCs (T + DCs) (n = 10) animals inoculated with 4T1 tumoral lineage and subsequently treated with dendritic cells, group V, tumor treated with IFN-α (T + IFN-α) (n = 10) animals with inoculation of 4T1 tumoral lineage and subsequently treated IFN-α, and group VI, tumor treated with IFN-α and DCs vaccine (T + IFN-α + DCs) (n = 10) animals inoculated with 4T1 tumoral lineage and subsequently treated with IFN-α and DCs vaccine. We can observe that the induction of tumor, on the immunotherapy groups combined with Interferon-α and DC's, and also on immunotherapy isolated only with Interferon-α, reduces the quantities of lymphocytes and also lymphocytes producers of Th1 cytokines, peritoneal macrophages and increases the presence of Th2 cytokines and Treg cells. The results also demonstrated that the DCs, even in the presence of the tumor, group (T + DCs) was able to promote a decrease in the expression of the proteins involved in vascular microdensity (CD31), (CD105) and in cell proliferation (Ki-67). It was also possible to observe an increase in the expression of intratumoral CD4+ and CD8+ lymphocytes in the group treated with DCs vaccine in the presence of the tumor. Therefore we can conclude that tumor microenvironment seems to have a negative strong influence on the effector action of Interferon-α. On the contrary, only presence of the DC's on the tumor promoted immune system polarization toward an anti-tumor Th1 response pattern profile. Nevertheless, more studies are needed to seek the best understanding of the biology and adjuvant action of IFN-α together with dendritic cells.Universidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeMICHELIN, Márcia Antoniazi11828808865http://lattes.cnpq.br/2599409028588669BORGERS, John Paul47668032649http://lattes.cnpq.br/5724192420139830ALEIXO, André Adriano Rocha2019-07-17T20:35:56Z2018-06-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfALEIXO, André Adriano Rocha. 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The Role of the Tumor Microenvironment in Regulating Angiogenesis The Role of the Tumor Microenvironment in Regulating Angiogenesis. 2013.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-07-22T18:11:02Zoai:bdtd.uftm.edu.br:tede/772Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2024-04-24T09:59:47.600633Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
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