This study examined whether 1-methyl-tryptophan [1-MT, an indoleamine 2, 3-dioxygenase (IDO) inhibitor] could reduce CD4+CD25+ regulatory T cells (Tregs) proliferation and improve the anti-
tumor efficacy of dendritic cells (DCs) pulsed with
tumor cell lysate in the mice bearing pancreatic
adenocarcinoma. The models of pancreatic
adenocarcinoma were established in C57BL/6 mice by
subcutaneous injection of Pan02 cells. Eight mice which were subcutaneously injected with PBS served as control. The expression of IDO was determined in
tumor draining lymph nodes (TDLNs) and spleens of the murine pancreatic
adenocarcinoma models. The prevalence of Tregs was measured in the TDLNs and spleens before and after 1-MT administration. The dendritic cells were pulsed with
tumor cell lysate for preparing DC
vaccine. The DC
vaccine, as a single agent or in combination with 1-MT, was administered to pancreatic
adenocarcinoma mice. The anti-
tumor efficacy was determined after different treatments by regular observation of
tumor size. The results showed that the levels of IDO
mRNA and
protein in
tumor-bearing mice were significantly higher than those in the normal control mice. The percentage of Tregs in the spleen and TDLNs was also higer in
tumor-bearing mice than in normal control mice (P<0.05). Foxp3 expression was significantly lower in the TDLNs and spleens of
tumor-bearing mice administrated with 1-MT than that in normal control mice. Furthemore, in the mice that were administered 1-MT plus DC
vaccine, the
tumor was increased more slowly than in mice treated with DC
vaccine or 1-MT alone, or PBS on day 36 (P<0.01). Our results indicated that 1-MT may enhance anti-
tumor efficacy of dendritic cells pulsed with
tumor cell lysate by downregulating the percentage of Tregs.