Clinical Significance Of Myeloid-derived Suppressor Cells In Breast Cancer Patients And Study On Immunospression Mechanisms

Objective:This study aimed to explore the secretion of indoleamine-2,3-dioxygenase (IDO) in myeloid-derived suppressor cells (MDSC) and its role in immunosuppression. Moreover, we analyzed the relevant impact of MDSC on T cell proliferation and cytokine secretion.Methods:Peripheral blood samples were obtained from30breast cancer patients and30healthy volunteers from the Tianjin Medical University Cancer Institute and Hospital. Breast cancer samples were also acquired from the patients. T cells from the peripheral blood of healthy volunteers and MDSC from the primary focus of the tumor were separated through a magnetic cell sorting system. IDO expression was determined using Western blot and PCR separately. MDSC-induced T cell apoptosis was detected by flow cytometry. We investigated the role of IDO in MDSC immunosuppression using1-MT. Cytokine secretion was determined by ELISA.Results:The percentage of MDSC in healthy peripheral blood, breast cancer patient peripheral blood and breast tumor tissue is(4.9±4.38)%,(12.92±6.24)%,(17.18±5.19)%. The percentage of MDSC in breast cancer patient peripheral blood and breast tumor tissue is higher than in healthy peripheral blood (P＜0.05). We found up-regulated IDO expression in MDSC. T cell apoptosis in the group with T cell culture alone, the group with co-culture of MDSC and T cell, and that with co-culture of MDSC, T cell, and1-MT was (2.40±0.66)%,(12.30±0.80)%, and (3.30±0.58)%, respectively. There were significant differences in the T cell apoptosis rate between the group with T cell culture alone and co-culture of MDSC and T cell. The tumor-derived MDSC could promote TGF-β and IL-10secretion and could inhibit IFN-y secretion dramatically. However, the differences in the secretion of IL-4and IL-12were not statistically significant. After incubation with1-MT, the differences in apoptosis rate between the T cell-alone culture group and the incubation group were not significant.Conclusion:IDO expression is upregulated in MDSC from the primary site of breast cancer. The tumor-derived MDSC inhibited IFN-ysecretion dramatically and promote TGF-β, IL-10secretion. The upregulation of IDO expression may be an important mechanism for the immunosuppression of MDSC.