Moléculas de adesão em metástases pulmonares e hepáticas de tumor de mama experimental submetidos à imunoterapia com vacina de células dentríticas.

Abstract

Both metastasis and the processes involved in the spread of cancer cells from the primary lesion to other organs encompass a variety of mechanisms that include invasion or coexistence with the stroma and escape from the surveillance of the immune system that inhibits or associates its antitumor processes. Adhesion molecules have been studied in order to understand their role in breast cancer, in order to relate these findings to therapeutic development since some of these molecules have activation and cell migration functions that directly influence the pro-inflammatory immune response. inflammatory. Studies published by our research group demonstrate that preventively administered dendritic cell (DC) vaccine has the ability to reduce lung and liver metastases. However, it remains to be clarified whether adhesion molecules could be involved in this reduction. Among the objectives of the study, we sought to analyze whether the presence of adhesion molecules CD40, CD54, CD62L, CD102, CD106 and CD152 in the lung and liver of the vaccinated group is correlated with the metastatic reduction in these organs, as well as to assess the levels of nitric oxide and the concentration of the cytokines IL-1β, IL-6 and TNF-α. For this, 25 female mice of the isogenic Balb/c strain were used, where 7 animals were separated for a control group free of interferences, and 3 animals were used for the preparation of dendritic cell vaccine. The remaining animals were divided into 2 groups, a group vaccinated prophylactically (n = 7) and submitted to tumor induction and another group with animals submitted only to tumor induction (n = 8), with liver and lung samples from both animals being used. groups, as well as splenic cell samples. The paraffin-embedded liver and lung samples were later analyzed by Immunofluorescence technique to investigate the adhesion molecules, while another part was submitted to the protein extraction process for analysis through the ELISA technique. The dosages and nitric oxide were carried out in the splenic cell culture supernatant. The results showed that the Mean Fluorescence Intensity (MFI) is increased in the molecules CD40 (p=0.0023), CD54 (P=0.0030), and CD152 (p < 0.0001) in the livers of the vaccinated group. and without statistical significance in the CD106 molecule (p = 0.1585) from the same group. On the other hand, CD62L (p <0.0001) and CD102 (p <0.0001) molecules were increased in liver samples from the group that was not vaccinated. As for lung sample analyses, there was an increase in CD62L (p < 0.0001), CD102 (p < 0.0001) and CD152 (p < 0.0001) molecules in the vaccinated group. There was no statistically significant difference in CD40 (p = 0.2876) and CD106 (p = 0.8070) in the same group. The increase in lung samples from the non-vaccinated group was seen in the CD54 molecule (p = 0.0010). Regarding the 11 levels of nitric oxide, the values were found to be increased in the vaccinated group of the culture stimulated with LPS (p = 0.0576). The cytokine IL-1β was increased in the liver of the vaccinated group (p < 0.0046), the cytokine IL-6 did not show statistical relevance in both organs of the group (p < 0.4818) and the cytokine TNF- also in both organs in the group (p < 0.0982). These findings guide the understanding of the importance of a mechanism that promotes the balance of the expression of these adhesion molecules in the body, so that there is an adequate and efficient leukocyte targeting during the antitumor fight. And dendritic cells being effective mediators of the response activated by T lymphocytes demonstrated involvement in this cellular targeting. Therefore, prophylactic vaccination with dendritic cells (DCs) has the ability to modulate the antitumor response even without prior specific stimulation of adhesion molecules, which in turn have the ability to direct the migratory behavior of tumor cells.