Caracterização fenotípica das células TDC em camundongos com câncer de mama

Abstract

TDC cells represent a rare cluster of hematopoietic cells with phenotypic and functional characteristics of dendritic cells and T lymphocytes. In this work, we evaluate the expression of surface markers (CD4 e CD8), transcription factors (Tbet, Foxp3, Gata3 e Rorγt), and cytokines (IFN-γ, TNF-α, IL10, IL-12 e IL-17) in TDC αβ cells in liver, lymph node, bone marrow and tumour. We also identify and characterize TDC γδ cells and the effect of the tumor on these cells in healthy mice (control) and induced to the development of cancer by 4T1 cells, through the flow cytometry technique. We note that TDC αβ are more frequent in lymph nodes of both groups studied 70.05 (52.78-87.32) e 67.02 (67.02 – 97.88) (p<0.0001). We noticed, decreased expression of TDC CD4 in the liver 1662 (1551- 1662) (p=0.0001), TDC CD8 in the spleen 764.7 (485.8 - 1467) (p=0.0012) and liver 2078 (2078 – 2602) (p=0.0028) e TDC CD86 in the spleen3997 (1550 – 7700) and liver 2742 (2197 – 2742) (p=0.0337) 4T1-induced tumor group. Decrease of TDC Tbet and TDC Foxp3 spleen 1427 (704,1 – 1517) (p<0,0001); 1016 (962,9 – 2265) (p<0,0001) and liver 5338 (4804 – 5338) (p=0,0001); 5133 (5133–6077) (p=0,0337), respectively TDC Gata3 in liver 3346 (3346 – 5101) (p=0,0028) and increased TDC Rorγt in tumor 3340 (3223 – 3722) (p<0.0001) that same group. We have shown a decrease in TDC IFN-γ in spleen 1554 (705.3 – 1885) (p<0.0001) and bone marrow 733.1 (733.1 – 1307) (p=0.0002), TDC TNF-α in spleen 1655 (2673 -403.8) and bone marrow 819.2 (819.2 – 1521) (p<0.0001), TDC IL-10 in spleen 1689 (914,3 – 2049) (p<0.0001), liver 5219 (5219 – 5619) (p<0.0001) and bone marrow 894.0 (894.0 – 1712), IL-12 in spleen 1841 (360.7 – 2728) and bone marrow 791.0 (688.8 – 791.0) (p=0.0002) and IL-17 in spleen 578.5 (326.3 – 873.8) (p<0.0001) and liver 1200 (1200 – 1988) (p=0.0001) breast cancer-induced mice. We do not, the presence of 26.53% TDC γδ cells in the control groups and a higher percentage of cellsTDC αβ in the breast cancer-induced tumor group compared to breast cancer cells TDC γδ (p<0.0001). The proportions of citokines IFN-γ, TNF-α, IL-12 and IL-17 produced by TDC γδ are decreased in tumour conditions (p<0.0001). Phenotypic lt can be conducted by microenvironment and tissue in the presence of the tumor, theTDC γδ have immunological characteristics shared with the cells TDC αβ. Directions are necessary to understand the functionality associated with possible antitumor immunotherapy.