Avaliação da expressão dos fatores de transcrição em células tumorais e esplênicas de camundongos com carcinoma mamário induzido por 4T1 e submetidos à imunoterapia de células dendríticas associada com linfócitos T infiltrantes

Abstract

By definition, cancer is a disease in which some cells in the body grow uncontrollably and spread to other parts of the body. This situation is attributed to the formation of metastases, in which tumor cells detach from the primary site and migrate to other regions, which has a positive impact on prognosis and directly affects patient survival. Challenges in treating the disease persist, and a promising alternative is immunotherapy, which offers hope for improving survival for those who do not respond to conventional treatments. Dendritic cells, when presenting antigens, play a crucial role in stimulating the immune system with the activation of lymphocytes in the anti- tumor fight. The proposal is to integrate these two cells to improve the general effects of immunotherapies in an experimental model of mammary carcinoma induced by 4T1 cells. 70 female BALB/c mice aged 6 weeks were used, divided into 4 groups: control, tumor, tumor treated with TIL, tumor treated with DC+TIL. At the end of the experimental phase, the mice were euthanized. The tumor, spleen and liver were removed for evaluation. The influence on tumor volume was noted, with the animals having their tumors measured using a caliper during the experimental phase. Animals treated with immunotherapy had a smaller tumor volume compared to those that were not subjected to such intervention. We evaluated by flow cytometry the presence of lymphocytes of the Th1, Th2, Treg and Th17 profiles, through the presence of the transcription factors T-bet, GATA3, FOXP3 and RORγT, respectively, in the spleen and tumor. It was possible to evaluate the different behavior between systemic and local immunity, the groups that received immunotherapies obtained higher T-bet values, in the tumor microenvironment, a determining factor for the Th1 profile, which has a great capacity to combat tumors. We observed a reduction in the metastatic area in liver cells by HE in the treated groups. The study highlighted the efficacy of immunotherapy with TILs alone in BALB/c mice with 4T1 cell-induced mammary carcinoma. Furthermore, it showed an enhancement when combined with dendritic cell immunotherapy, which resulted in the regression of tumor volume and metastatic points in the liver.