Papel da resposta imune celular da obesidade na progressão do carcinoma mamário experimental

Abstract

Nowadays the obesity is a public health issue capable to affect all ages, social classes, and regions of the globe. According to data from Word Health Organization in 2014, 13% of the adult population is considered obese. In Brazil the number are also startling: in the adult population 12.4% of the men and 16.9% of women already was considered obese in 2011 by Ministry of Healthy. Breast cancer is the only one diagnosed in all regions of the planet and, according to American Society of Cancer, in 2012 this type of cancer was responsible for 25% of the new cases and killed more than half millions of women. The Brazilian women undergo by breast cancer, which is the most commonly diagnosed among Brazilian women, according data from Nacional Institute of Cancer in 2015. Is certain that the obesity duplicates the chances to develop breast cancer and it is correlated to the low grade chronic inflammation established by the fat accumulation which recruit inflammatory cells that secrete cytokine, chemokines, and growth factors, increasing the inflammation. In this context the malignant mammalian cells get hold of this inflammation and its mediators to promote its own survival, proliferation, dissemination, and metastasis. To identify the role of the obesity in malignant breast tumor, we utilized in this project the experimental murine model of breast cancer 4T1 in animals Balb/c females feed for 16 weeks with the pattern diet or high-fat diet which 60% of kilocalories coming from lipids. Each animal was weekly weighed and the individual average intake was calculated. At the end of the 16 weeks more 21 tumor days after injection, the animals were euthanized for removal of the perigonadal and retroperitoneal fat-pad and also for the removal of the draining inguinal lymph nodes of the tumor to flow cytometry analysis. The results indicate that the animals feed with HFD, had weight gain even eating less than the animals feed by control diet. This gain reflected in a major adiposity in obese animals due to higher weight of the perigonadal and retroperitoneal fat-pad. Moreover, the obese animals had a higher Lee Index on comparison of the controls animals. Our work indicated a general decrease in the immune response against the tumor because was observed a decay of the number of the total cells of the tumor lymph nodes drainage, which reflected a low number of macrophages and dendritic cells, which also presents a lower activation with low expression of co-stimulators CD80 and CD86; and a decrease in the number of cells from adaptive response effector and in regulator cells like lymphocytes Breg and Treg. In addition, was also observed an unbalancing between the inflammatory cytokine IFNv and the anti-inflammatory cytokine IL-10, produced by lymphocytes CD4+ and CD8+. Together, this data allowed us to conclude that the obesity directly affect the immune system through the reduction of the cellular response against the tumor, this setting can be due to modulation of hematopoiesis and induction of MDSC.