Análise do perfil funcional das células dendríticas usadas na imunoterapia do câncer de mama induzido por células 4T1 em camundongos BALB/c Uberaba

Abstract

Dendritic cells (DCs) are considered the best antigen-presenting cells and can develop potent cytotoxic activity, characterizing them as killer dendritic cells. These cells are often used in studies for cancer treatment, a group of diseases originating from the uncontrolled growth of cells. In the past, DCs were used due to their excellent antigen presentation ability; today, their cytotoxic capacity is also considered. Given this other characteristic, it became imperative to investigate the fate and function of these cells, obtained through a standardized differentiation and maturation protocol at the Oncology Research Institute (IPON). Furthermore, efforts were made to understand the indirect effector mechanisms of DCs in combating tumor cells. To conduct these studies, female BALB/c mice were induced to develop breast cancer using 4T1 cells. Subsequently, they were treated with DC immunotherapy labeled with CFSE. During the experimental period, DCs were monitored in vivo, and after euthanizing the animals, markings were made on the lymph nodes for MHC-II, helper T cells, and cytotoxic T cells. It was observed that DCs migrated to the lymphatic organs, where they performed their antigen-presenting function. When analyzing the indirect effector functions of DCs in tumors, through the expression of granzyme B, perforin, Fas, and FasL using direct immunofluorescence technique, a significant decrease in the expression of granzyme B, perforin, and Fas was found in the treated animals' tumors compared to the untreated ones. Additionally, an increase in FasL was observed in the treated group compared to the untreated control group. Besides these results, a reduction in tumor volume was evidenced, suggesting that this decrease was not triggered solely by granzyme B and perforin but also by the decrease in Fas and increase in FasL in the treated animals' tumors. Thus, it is inferred that in the model studied here, DCs acted as excellent antigen-presenting cells, not only performing the presentation function but also effectively contributing to the cytotoxic response in the tumor environment.