Title |
INFα-2b inhibitory effects on CD4+CD25+FOXP3+ regulatory T cells in the tumor microenvironment of C57BL/6 J mice with melanoma xenografts
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Published in |
BMC Cancer, July 2016
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DOI | 10.1186/s12885-016-2473-0 |
Pubmed ID | |
Authors |
Yang Yu, Run Huang, Xiangyun Zong, Xiangming He, Wenju Mo |
Abstract |
Regulatory T cells (Tregs), particularly the CD4(+)CD25(+)Foxp3(+) Tregs, 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. 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 Tregs 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. 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(+) Tregs to lymphocytes and CD4(+) cells in the spleen and in peripheral blood were significantly decreased after treatment with IFNα (P < 0.05). Expression of TGFβ and IL-10 in the tumor microenvironment in the CT and RT groups was higher compared with the control group (P < 0.01), while the expression of TGFβ and IL-10 in the INFα group was not significantly different (P > 0.05). The results show that INFα-2b inhibits cancer cell immune evasion by decreasing the levels of CD4(+)CD25(+)Foxp3(+) Tregs and suppressing the expression of TGFβ and IL-10 in the tumor microenvironment. |
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