白细胞介素-7 通过促进 T 细胞介导的抗肿瘤免疫抑制 Meth A 模型中的肿瘤生长。

IL-7 inhibits tumor growth by promoting T cell-mediated antitumor immunity in Meth A model.

机构信息

Department of Biochemistry, North Sichuan Medical University, China.

State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.

出版信息

Immunol Lett. 2014 Mar-Apr;158(1-2):159-66. doi: 10.1016/j.imlet.2013.12.019. Epub 2014 Jan 7.

DOI:10.1016/j.imlet.2013.12.019

PMID:24406503

Abstract

Immune suppression is well documented during tumor progression, which includes loss of effect of T cells and expansion of T regulatory (Treg) cells. IL-7 plays a key role in the proliferation, survival and homeostasis of T cells and displays a potent antitumor activity in vivo. In the present study, we investigated the antitumor effect of IL-7 in Meth A model. IL-7 inhibited tumor growth and prolonged the survival of tumor-bearing mice with corresponding increases in the frequency of CD4 and CD8 T cells, Th1 (CD4(+)IFN-γ(+)), Tc1 (CD8(+)IFN-γ(+)) and T cells cytolytic activity against Meth A cells. Neutralization of CD4 or CD8 T cells reversed the antitumor benefit of IL-7. Furthermore, IL-7 decreased regulatory T Foxp3 as well as cells suppressive activity with a reciprocal increase in SMAD7. In addition, we observed an increase of the serum concentrations of IL-6 and IFN-γ, and a significant decrease of TGF-β and IL-10 after IL-7 treatment. Taken together, these results indicate that IL-7 augments T cell-mediated antitumor immunity and improves the effect of antitumor in Meth A model.

摘要

免疫抑制在肿瘤进展过程中得到了充分证实，其中包括 T 细胞效应丧失和 T 调节（Treg）细胞扩增。IL-7 在 T 细胞的增殖、存活和稳态中发挥着关键作用，并在体内显示出强大的抗肿瘤活性。在本研究中，我们研究了 IL-7 在 Meth A 模型中的抗肿瘤作用。IL-7 抑制肿瘤生长，延长荷瘤小鼠的生存时间，相应增加 CD4 和 CD8 T 细胞、Th1（CD4+IFN-γ+）、Tc1（CD8+IFN-γ+）和 T 细胞对 Meth A 细胞的细胞毒性。CD4 或 CD8 T 细胞的中和作用逆转了 IL-7 的抗肿瘤益处。此外，IL-7 降低了调节性 T 细胞 Foxp3 以及细胞抑制活性，同时 SMAD7 增加。此外，我们观察到 IL-7 治疗后血清中 IL-6 和 IFN-γ 的浓度增加，TGF-β 和 IL-10 的浓度显著降低。综上所述，这些结果表明，IL-7 增强了 T 细胞介导的抗肿瘤免疫，并改善了 Meth A 模型中的抗肿瘤效果。