Li Yuandong, Xu Jun, Zou Haojun, Wang Chunyou
Pancreatic Surgery Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2010 Jun;30(3):344-8. doi: 10.1007/s11596-010-0354-3. Epub 2010 Jun 17.
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.
本研究检测了1-甲基色氨酸[1-MT，一种吲哚胺2,3-双加氧酶（IDO）抑制剂]是否能减少荷胰腺腺癌小鼠中CD4+CD25+调节性T细胞（Tregs）的增殖，并提高用肿瘤细胞裂解物脉冲处理的树突状细胞（DCs）的抗肿瘤疗效。通过皮下注射Pan02细胞在C57BL/6小鼠中建立胰腺腺癌模型。八只皮下注射PBS的小鼠作为对照。测定小鼠胰腺腺癌模型的肿瘤引流淋巴结（TDLNs）和脾脏中IDO的表达。在给予1-MT之前和之后，测量TDLNs和脾脏中Tregs的比例。用肿瘤细胞裂解物脉冲处理树突状细胞以制备DC疫苗。将DC疫苗单独或与1-MT联合给予胰腺腺癌小鼠。通过定期观察肿瘤大小来确定不同处理后的抗肿瘤疗效。结果显示，荷瘤小鼠中IDO mRNA和蛋白水平显著高于正常对照小鼠。荷瘤小鼠脾脏和TDLNs中Tregs的百分比也高于正常对照小鼠（P<0.05）。给予1-MT的荷瘤小鼠的TDLNs和脾脏中Foxp3表达明显低于正常对照小鼠。此外，在给予1-MT加DC疫苗的小鼠中，在第36天时肿瘤生长比单独用DC疫苗或1-MT或PBS处理的小鼠更慢（P<0.01）。我们的结果表明，1-MT可能通过下调Tregs的比例来增强用肿瘤细胞裂解物脉冲处理的树突状细胞的抗肿瘤疗效。
