INFα-2b inhibitory effects on CD4 + CD25 + FOXP3 + regulatory T cells in the tumor microenvironment of C57BL/6?J mice with melanoma xenografts

摘要

Background Regulatory T cells (Treg_s), particularly the CD4+CD25+Foxp3+ Treg_s, down regulate immunity and promote tumor cell growth by directly suppressing CD8+ and CD4+ T cells. Alternatively they can promote tumor growth by generating interleukin-10 (IL-10) and transforming growth factor β (TGFβ) in situ, which help tumor cells to evade the immune system. Methods In vivo tumor models were prepared via subcutaneous injection with a suspension of B16 melanoma cells into the left upper flank of C57BL/6?J mice. The mice were randomized into five groups: radiotherapy (RT), chemotherapy (CT), radiochemotherapy (RCT), Inteferon α (INFα) groups, and a control group. Flow cytometry was used to determine the Treg_s levels in the spleen and peripheral blood, and immunohistochemistry was performed to determine the expression levels of TGFβ and IL-10 in the tumor microenvironment. Results Tumor weight was significantly reduced in the CT or RCT groups (40.91?% and 41.83?%, respectively), while the reduction in tumor weight was relatively lower for the RT and IFNα groups (15.10?% and 13.15?%, respectively). The flow cytometry results showed that the ratios of CD4+CD25+Foxp3+ Treg_s to lymphocytes and CD4+ cells in the spleen and in peripheral blood were significantly decreased after treatment with IFNα ( P ?0.05). Conclusions The results show that INFα-2b inhibits cancer cell immune evasion by decreasing the levels of CD4+CD25+Foxp3+ Treg_s and suppressing the expression of TGFβ and IL-10 in the tumor microenvironment.