摘要
Regulatory T （Treg） cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8＋ Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8＋ Treg cells in ovarian cancer （OC） patients. Here, we investigated CD8＋ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8＋ T cells and the forkhead box p3 （Foxp3）＋ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8＋ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8＋ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including a n increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 （CTLA-4）, and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8＋ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8＋ T cells cultured alone, the CD8＋ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8＋ Treg cells inhibited naive CD4＋ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8＋ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.
Regulatory T （Treg） cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8＋ Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8＋ Treg cells in ovarian cancer （OC） patients. Here, we investigated CD8＋ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8＋ T cells and the forkhead box p3 （Foxp3）＋ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8＋ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8＋ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including a n increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 （CTLA-4）, and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8＋ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8＋ T cells cultured alone, the CD8＋ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8＋ Treg cells inhibited naive CD4＋ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8＋ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.
