| AimOvarian cancer(OC) is one of the tumors associated with the highest morbidity and mortality. It is the most common gynecologic tumor, clinically characterized by high recurrent rates and poor prognosis. Immunotherapy holds much promise for the treatment of cancer. However, most immunotherapeutic approaches on their own are of limited value against the majority of malignancies. The tumor microenvironment can inhibit immune responses leading to ineffective or suboptimal responses of tumors to immunotherapy in the majority of cases. In this study, we aimed to investigate the expression of CD33+ HLA-DR-/low myeloid-derived suppressor cells(MDSCs), regulatory T cells(Tregs),Th1 and Th2 cytokines, and their correlations with clinical pathological parameters. We further tended to disclose the potential mechanisms these immuno suppressive cells mediated in OC in order to supplement more ways about the immunotherapies towards immune escape.Methods72 cases of ovarian cancer(OC) patient and 30 cases of health individual as control were enrolled in this study. Flow cytometry was used to investigate the prevalence of CD33+ HLA-DR-/low MDSC, CD4+CD25+CD127-/low Treg in the peripheral blood of patients with OC and 30 healthy controls. The correlations of Treg and MDSC with clinical pathological factors were analyzed statistically. The expression of Th1 and Th2 cytokines were evaluated by using BD Cytometric Bead Array(CBA) analysis and their correlations with clinical pathological factors were further investigated.Results1. MDSC cells are CD33+ HLA-DR-/low. The level of MDSC in the peripheral blood of patients with OC(3.391±1.931)% was significantly increased(P<0.01), compared with the health controls(0.762±0.214)%. The expression of MDSC was significantly correlated with pathological grade and clinical stage,but not age, tumor size and pathological type. After surgery to move out the tumor, the level of MDSC was downregulated(2.019±1.034)% obviously(P<0.05).2. Treg cells are CD4+CD25+ CD127-/low. The level of Treg in the peripheral blood of patients with OC(14.068±4.546)% was significantly increased(P<0.01), compared with the health controls(5.051±1.170)%. The expression of Treg was significantly correlated with and clinical stage, but not age, tumor size,pathological grade and type. After surgery to move out the tumor, the level of Treg was downregulated(12.243±4.213)%(P<0.05).3. Significant correlation between CD33+HLA-DR-/low MDSC and CD4+CD25+CD127-/low Treg in the peripheral blood of patients with OC was observed(n=72, r=0.0563, P<0. 05).4. The level of Thl-type cytokines IL-2 and IFN-γ in the peripheral blood of patients with OC was significantly decreased(P < 0.01), compared with the health controls(P < 0.01), the level of Th2-type cytokines IL-6 and IL-10 was significantly increased(P < 0.01), while IL-4 and INF-γ were not statistically significant between the OC groups and the health groups. The level of IL-4 and INF-γ in the peripheral blood of patients with early tumor was significantly increased(P<0.01), compared patients with the advanced tumor, meanwhile, the IL-6 and IL-10 level in OC patients with early tumor were obviously lower than in OC patients with advanced tumor.ConclusionsThe level of CD33+HLA-DR-/low MDSCs and CD4+CD25+ CD127-/low Tregs in the peripheral blood of patients with OC were significantly increased compared with the health controls, with significant correlation between circulating MDSC and Treg was observed. Decreased level of Thl-type cytokine and increased Th2-type cytokine in the peripheral blood of patients with OC suggest that the immune suppression wasformed. The results of this study provided experimental basis and methods for reversing the immunologic deficiency and improving the prognosis of patients with OC. |
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