1-MT enhanced potency of dendritic cells pulsed with tumor cell lysate by downregulation of CD4 ~+ CD25~+ treg

Abstract

Objective To determine whether 1-methyl-tryptophan (1-MT, an IDO inhibitor) might reduce CD4~+ CD25~+ Treg and improve the anti-tumor effects of dendritic cells pulsed with tumor cell lysate in the murine pancreas adenocarcinoma model. Methods Pan02 cell line was injected into syngeneic C57BL/6 mice. 1-MT was administered to pancreas adenocarcinoma mice and its effect on the prevalence of regulatory T cells (Treg) in tumor draining lymph nodes (TDLNs) and spleen was investigated. The prevalence of Treg in the TDLNs and tumor spleen (TS) was detected by using flow cytometry. The expression level of Foxp3 mRNA was detected in the spleen and TDLN by real-time PCR. To prepare the DC vaccine,dendritic cells were pulsed with tumor cell lysate. This DC vaccine, as a single agent or in combination with 1-MT, was administered to pancreas adenocarcinoma mice. The anti-tumor effects in different treatment were deter mined by regular observation of tumor development. Results There was statistically significant difference in the percentage of CD4~+ CD25~+ T lyraphocytessignificant between 1-MT-treated group [TDLNs (16.01 ± 2.21)% and TS (13. 11 ± 1. 93)%] than PBS control group [TDLNs (25. 00 ± 2. 16)% and TS (22.14 ±2.33)%] (P<0.05,P<0.01). In 1-MT-treated group,the Foxp3 expression was significantly lower in TDLN and TS than in control LN and spleen. Furthemore,in 1-MT + DC vaccine-treated group,the tumor growth rate was significantly slower than in groups of DC vaccine, 1-MT and PBS (the tumor volume was (789.0 ±111.0), (1768.0 ±251. 3), (1854.0 ±192. 1),(1899.0 ±201.2) mmJ at the 36th day af ter tumor challenge, respectively (P < 0. 01). Conclusion 1-MT can enhance anti-tumor effects of den dritic cells pulsed with tumor cell lysate by downregulating the expression of CD4~+ CD25~+ Treg. Key words: Pancreas adenocarcinoma; Dendritic cells; Vaccine