Avaliação espaço-temporal de subpopulações de linfócitos B em modelo de câncer de mama murino

Abstract

Breast cancer affects an expressive number of women worldwide according to data from the World Health Organization, being expected an increase in the number of cases in the coming decades. Risk factors such as advanced age, alcohol consumption, overweight, family history, age of menarche and menopause, contraceptive use and other factores are intimately associated with emergence of breast cancer. Among the subtypes, triple-negative breast cancer is considered the most severe form and associated with worst prognosis. Increased number of studies have identified the presence of distinct cell types in the tumor infiltrate. Although studies have evidenced the importance of T lymphocytes in tumor infiltrates, divergent data in found regarding B lymphocyte infiltrates in breast cancer. In addition, there are few studies that have evaluated the kinetics of B lymphocytes in function of breast tumor development. In the current study, we showed that the B cell compartment present in the spleen, inguinal lymph node and tumor respond differently in function of 4T1 tumor growth in BALB/c mice, demonstrating that distinct mechanisms possible act on the evaluated tissues. While a small change in B lymphocytes (CD19+ B220+) was noted in the spleen and tumor, a significant increase os this phenotype was observed in the inguinal lymph node soon after 7 days of transplantation of 4T1 cells. Though different subpopulations of B lymphocytes have been noted in the tumor infiltrate - such as naïve B cells, plasmablasts and regulatory B lymphocytes - the continuous elevation of intratumoral plasma cells (CD19- B220- CD138+) deserves to be highlighted. Taking into account that the establishment of an effective immune response depends on the continuous transportation and interaction of B lymphocytes with other cellular components, a better understanding of the kinetics of these cells is the initial step in elucidating potential acting mechanisms underlying breast tumor growth. Moreover, the better understanding of B cell dynamics may be crucial for the design of new therapeutic approaches for the treatment of the disease.