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

•Traf6 inhibitor slows Hepa1-6 tumor growth in immunocompetent mice.•Traf6 inhibitor impedes migration of Treg cells into tumor and therefore augments T cell-based antitumor immunity.•Traf6 inhibitor cooperates with PD-1 blockade to drive tumor rejection. 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.