Oridonin inhibits 4T1 tumor growth by suppressing Treg differentiation via TGF-β receptor

•Oridonin inhibits 4T1 tumor growth in vivo.•Oridonin suppresses Treg differentiation in vitro.•Oridonin decreases Treg differentiation in a TGF-β receptor dependent manner.•Combination oridonin and anti-PD-1 has superior 4T1 tumor regression. The Chinese herbal medicine oridonin has potent anti-inflammatory and antitumor activities. In addition, oridonin treatment effectively suppresses breast cancer growth. However, the underlying mechanisms are poorly defined. Here, we reported that oridonin decreased Treg differentiation in vitro and in vivo. Oridonin inhibition of Treg differentiation was dependent on decreasing TGF-β receptor expression. Oridonin attenuated Tregs’ immunosuppressive ability; thus, oridonin did not inhibit CD8+ T cell proliferation very well in vitro. Oridonin greatly delayed the progression of 4T1 tumors in vivo. In addition, oridonin combined with anti-PD-1 activated a robust antitumor immune response and suppressed 4T1 tumor growth. Therefore, our results indicate that oridonin inhibits TNBC growth by modulating Treg differentiation, which provides new directions for the clinical treatment of TNBC.