Objective      To determine the effect of the transmembrane TNF-α/tumor necrosis factor receptor 2  (tmTNF-α/TNFR2) signaling axis on the growth of transplantation tumor in mouse xenograft model and investigate the underlying mechanism.       Methods      Western blotting was used to determine the expression of TNFR1 and TNFR2 in the Treg cells from control mice and H22 tumor-bearing mice. TNFR2 knock-out mice and wild-type mice (10 animals in each group) were subcutaneously inoculated with H22 hepatocarcinoma cells

then the tumor grow

th as well as the accumulation of Treg in the suspension of tumor cells were observed. IL-10 and TGF-β production in Treg cells in response to the exogenous tmTNF-α were detected by ELISA.       Results      The TNFR2 expression was significantly higher in the Treg cells from the tumor microenvironment in the tumor-bearing mice than in the spleen Treg cells from wild-type mice (P0.05)

but no significant change was seen in the TNFR1 expression. Tumor size was obviously smaller in the TNFR2

-/-

tumor-bearing mice than the wild-type tumor-bearing mice (P0.05)

and the percentage of Treg in the tumor microenvironment was remarkably less in the former group of mice than the latter (P0.05). Exogenous tmTNF-α promoted the secretion of IL-10 and TGF-β in Treg cells (P0.05).       Conclusion       The transplanted tumor gowns slowly in TNFR2 knockout mice

with reduced Treg cells in the tumor microenvironments. tmTNF-α stimulates the release of anti-inflammatory cytokines IL-10 and TGF-β in the Treg cells to enhance the immune response.