The role of stromal mast cells in the modification of CD4⁺CD25⁺Foxp³ regulatory T cells, Th17 lymphocytes and cytotoxic lymphocytes Tc1 in the development and progression of tumor

摘要

Despite the lack of direct evidence that immune surveillance cells protect against tumor development, indirect clinical observations and experimental studies indicate activity in the immune response against cancer cells of various origin. Little is known about the effects of the stromal tumor mast cell (MC) in the activity of immune cells, i.e. CD4⁺CD25⁺Foxp3⁺ regulatory T cells, Th17 lymphocytes, cytotoxic lymphocytes Tc1 and their mutual modulatory function and regulation of the antitumor immune response. Factors synthesized by stromal tumor mast cells including histamine, COX-2, CXCL8 (IL-8), VEGF, IL-6, TNF, iNOS, MMP-8, and MMP-9 may, on the one hand, directly affect the activity of T lymphocyte subpopulations, i.e. iTreg, Tc1, and Th17, and thus regulate immunological processes occurring in the vicinity of the tumor. On the other hand, through effects on angiogenesis, apoptosis, the cell cycle, secretion of cytokines and the expression of adhesion molecules, they may indirectly determine the progression of the neoplasm. Understanding the regulatory mechanisms occurring in the system: tumor stroma mast cell → immune cells infiltrating the tumor (iTreg, Tc1, Th17 lymphocytes) → expression of factors involved in angiogenesis, apoptosis, the cell cycle, and secretion of cytokines and adhesion molecules creates the future possibility of influencing the activation and regulation of selected proneoplastic and antineoplastic factors appearing in the neoplasm environment. Research on these mechanisms may be the beginning of a new approach to the fight against cancer growth and provide an opportunity to introduce new methods of treatment. The aim of this study was to present the current knowledge on the role of stromal tumor CD117⁺ mast cells and factors secreted by these cells in the activation of T lymphocyte subpopulations, i.e. CD4⁺CD25⁺Foxp3⁺ regulatory T cells, Th17 lymphocytes, and cytotoxic lymphocytes Tc1, as well as to present their impact on the degree of tumor invasiveness by regulating the synthesis of factors secreted by the lymphocyte subpopulations studied, e.g. IL-10 and TGF-β (iTreg), IL-17A and IL-6 (Th17), IFN-γ and IL-2 (Tc1).