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

Abstract

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). 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).

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.

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