1-MT enhances potency of tumor cell lysate-pulsed dendritic cells against pancreatic adenocarcinoma by downregulating the percentage of Tregs.
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.
Li
Yuandong
Y
Pancreatic Surgery Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. l9345972@126.com
Xu
Jun
J
Zou
Haojun
H
Wang
Chunyou
C
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D015536:Down-Regulation; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D019496:Cancer Vaccines; D014364:Tryptophan