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 combinada

Abstract

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.