Análise do perfil de macrófagos peritoneais obtidos de camundongos com tumores de mama induzidos por células 4T1 submetidos à imunoterapia com células dendríticas

Abstract

The National Cancer Institute (INCA) brings breast cancer as the type of neoplasm that will be the most incident among women for the 2016-2017 biennium. The immune system has an important ability to eliminate neoplastic cells enunciated as immune surveillance, is to use the mechanisms of innate immunity and acquired immunity. Through the dendritic cells along with the macrophages and monocytes they form the first line of defense of the organism. In view of their important role in the face of tumors, dendritic cells have been an important target in immunotherapies research. Macrophages, important in immune surveillance but poorly studied in cancer immunotherapies, are classified into macrophages of the M1 profile, which may express tumor-fighting cytokines and macrophages of the M2 profile may express some tumor-favoring cytokines. In this sense, the present work proposes to analyze the peritoneal lavage of BALB / C mice, induced to breast cancer by 4T1 cells and treated with the dendritic cell vaccine. We used 70 BALB / c mice, 60 females and 10 of both genera for spinal cord extraction and dendritic cell vaccine preparation, the animals were divided into four groups with a n of 15 per group; who received no type of treatment, a group treated with dendritic cell vaccine, but without tumor inoculation, a tumor group in which the animals received the inoculation of the 4T1 tumor line, but did not receive treatment with the dendritic cell vaccine and the group treated tumor in which the animals received the inoculation of 4T1 tumor cell lines and subsequent treatment with the dendritic cell vaccine. The peritoneal lavage was analyzed by flow cytometry through extracellular and intracellular CD14 labeling for IL-10, IL-12, IFN-gamma, TNF-alpha, TGF-beta, IL-4 and IL-17 cytokines and the transcription, FOXP3, GATA3, ROR-gamma T and Tbet. Subsequently, culture of the supernatant of the peritoneal macrophages was performed and the concentration of IL-10, IFN-γ, IL-12 and IL-14 cytokines was measured by the ELISA technique. The results demonstrated that the dendritic cell vaccine was able to modulate the immune system by developing an antitumor and tumor-fighting response with a decrease in the concentration of pro-inflammatory cytokines (IL-12, IL-17, IFN-gamma, TNF- alpha) and anti-inflammatory and pro-tumor cytokines (IL-10, IL-4, TGF-beta), the expression of transcription factors can also be expressed in macrophages in all experimental groups, and have the lowest expression in the treated tumor group, when compared to the tumor group. It is concluded that the dendritic cell vaccine directs the immune system to combat cancer, which demonstrates a decrease in the expression of pro-inflammatory cytokines, systematically decreasing chronic inflammation and pro-tumor cytokines, demonstrating the effectiveness and action of immunotherapy with dendritic cells.