Traf6 inhibitor boosts antitumor immunity by impeding regulatory T cell migration in Hepa1-6 tumor model

Traf6 抑制剂通过阻碍 Hepa1-6 肿瘤模型中的调节性 T 细胞迁移来增强抗肿瘤免疫力

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作者:Xiao Wu, Rong Xue, Hao Peng, Xiaojie Gan, Xu Lu, Wei Yan, Yizhu Tian, Xuhao Ni, Hongbin Shen, Feng Cheng, Xuehao Wang, Xiaoming Wang, Ling Lu

Abstract

Tumors escape immune attacks via various mechanisms, among which activation of regulatory pathways in effector immune cells and recruitment of immunosuppressive cells are usually employed. Traf6 is a member of the family of tumor necrosis factor receptor-associated factors and involved in many signaling pathways. While it plays important roles in both tumor biology and immune system, the potential therapeutic role of Traf6 in tumor immunotherapy hasn't ever been assessed. Here, we confirmed the anti-tumor effect of Traf6 inhibitor in Hepa1-6 tumor model. Flow cytometry-based analysis revealed that T cell-mediated antitumor immunity was provoked and the infiltration of Treg cells was restrained when treated with Traf6 inhibitor. Via an in vivo migration assay, we found that Traf6 inhibitor decreased the population of intratumor Tregs by impeding the migration of Tregs towards tumor. Finally, we demonstrated that combination of Traf6 inhibitor and PD-1 blockade could receive a better antitumor efficiency. These results implicated that Traf6 inhibitor could serve as a supplement for immune checkpoint therapy.

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