Profilaxia por vacina de células dendríticas: avaliação de aspectos da resposta imunológica em camundongos Balb/c com carcinoma de mama induzido por 4T1

• Ano de defesa: 2021
• Autor(a) principal: VIEIRA, Jéssica Ferreira
• Orientador(a): MICHELIN, Marcia Antoniazi
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Triângulo Mineiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências da Saúde
• Departamento: Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
• País: Brasil
• Palavras-chave em Português: Imunoterapia.; Imunologia celular.; Célula dendrítica.; Vacinas anticâncer.; Neoplasias da mama.
• Palavras-chave em Inglês: Immunotherapy.; Cell immunology.; Dendritic cell.; Cancer vaccines.; Breast neoplasm.
• Área do conhecimento CNPq: Ciências da Saúde
• Link de acesso: http://bdtd.uftm.edu.br/handle/tede/1060

Dendritic cells (DCs) have been approached as a promising tool in the field of cancer immunotherapy, as they take advantage of the potency and specificity in inducing immune responses mediated by tumor-specific T cells. In this work, we investigated the influence of prophylactic immunotherapy with DC vaccine on the activation of the antitumor immune response, inhibition of metastasis, and cancer development, in an experimental model of breast cancer induced by 4T1. Twenty-five adult female Balb/c mice were used, separated into three experimental groups: control, tumor, and vaccinated, and the animals of the latter group received a single dose of DC vaccine before induction with 4T1 tumor cell cells. Throughout the experimental period, the animals had their tumor volumes measured periodically. We observed that the vaccine influenced the growth rate, by promote a reduction in tumor volumes. At the end of the experimental period, the animals were euthanized and the livers, lungs, spleens, and tumors of the experimental groups were evaluated. We observed a statistically significant reduction in the areas of liver and lung metastases in vaccinated animals compared to non-vaccinated animals, using the H&E technique. We found in the liver, by flow cytometry, that prophylaxis led to an increase in total T lymphocytes, T CTL, Treg, as well as IL-10 and IL-17 in Th; and reduction of Th1, Th2, Th17 and IL-12, IFN-γ, and TNF-α in Th. We performed a systemic evaluation, using spleen samples, by means of flow cytometry, in which prophylaxis also promoted an increase in lymphocytes. Total T, Th, and T CTL. Prophylaxis also promoted an increase in total T, Th, and T CTL lymphocytes. ELISA performed the evaluation of cytokines in this tissue after splenocyte culture and it was observed that only the cytokines IL-10 and IL-12 were significantly increased in the vaccinated group. An in vitro assay was also carried out with splenic cells under LPS stimulation for 12h, 24h, and 36h, that the cytokines present different secretion peaks. In the tumor microenvironment, we evaluated immune response cells, and prophylaxis with DCs increased Th, Th1, Th2, Th17, Treg, and T CTL cells, as well as IFN-γ and TNF-α in Th1 and T CTL cells. Investigative directions are necessary to understand the interaction and peculiarities of these processes. The prophylactic immunotherapy with dendritic cells acted differently in the different niches evaluated and demonstrated to alter the responses in these media, favoring the anti-tumor immune response.