Abstract:
Objective This study aimed to explore the secretion of indoleamine-2, 3-dioxygenase (IDO) in myeloid-derived suppressor cells (MDSCs) and its role in immunosuppression and to analyze the relevant impact of MDSCs on T cell proliferation and cytokine secretion.
Methods Peripheral blood samples were obtained from 30 breast cancer patients and 30 healthy volunteers from 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 MDSCs 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. The role of IDO in MDSC immunosuppression was investigated using 1-MT. Cytokine secretion was determined by ELISA.
Results Up-regulated IDO expression was found in MDSCs. T cell apoptosis in the group with T cell culture alone, the group with co-culture of MDSCs and T cell, and that with co-culture of MDSCs, T cell, and 1-MT was (2.90 ± 0.66) %, (12.30 ± 0.80) %, and (5.90 ± 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 MDSCs and T cell. The tumor-derived MDSCs could promote TGF-β and IL-10 secretion and could inhibit IFN-γ secretion dramatically. However, the differences in the secretion of IL-4 and IL-12 were not statistically significant. After incubation with 1-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 MDSCs from the primary site of breast cancer. The upregulation of IDO expression may be an important mechanism for the immunosuppression of MDSCs.