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1-MT Enhances Potency of Tumor Cell Lysate-pulsed Dendritic Cells against Pancreatic Adenocarcinoma by Downregulating the Percentage of Tregs

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第3期30卷 344-348页

作者：李元栋徐钧邹浩军王春友 Pancreatic Surgery Center of Union Hospital Tongji Medical CollegeHuazhong University of Science and Technology

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 *** models of pancreatic adenocarcinoma were established in C57BL/6 mice by subcutaneous injection of Pan02 *** mice which were subcutaneously injected with PBS served as *** expression of IDO was determined in tumor draining lymph nodes(TDLNs) and spleens of the murine pancreatic adenocarcinoma *** prevalence of Tregs was measured in the TDLNs and spleens before and after 1-MT *** dendritic cells were pulsed with tumor cell lysate for preparing DC *** DC vaccine,as a single agent or in combination with 1-MT,was administered to pancreatic adenocarcinoma *** anti-tumor efficacy was determined after different treatments by regular observation of tumor *** results showed that the levels of IDO mRNA and protein in tumor-bearing mice were significantly higher than those in the normal control *** percentage of Tregs in the spleen and TDLNs was also higer in tumor-bearing mice than in normal control mice(P1-MT than that in normal control ***,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(P1).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.

关键词： 1-methyl-tryptophan Treg cells pancreatic adenocarcinoma indoleamine 2,3-dioxygenase Foxp3

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Indoleamine 2,3-dioxygenase in tumor induced tolerance

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Chinese Medical Journal 2009年第24期122卷 3072-3077页

作者： LIU Xiao-qian WANG Xin Department of Hematology Provincial Hospital Affiliated toShandong University Jinan Shandong 250021 China

Objective To review the recent studies about the role of indoleamine 2,3-dioxygenase （IDO） in tumor induced tolerance. Data sources Published articles （1978-2009） on IDO and tumor induced tolerance were selected from Medline. Study selection Articles selected were relevant to development of IDO in tumor induced tolerance. Of all originally identified articles, 50 specially addressed the stated purpose. Results Recent work has revealed IDO at high levels in tumors and in tumor-draining lymph nodes and a close relationship between IDO activity and the regulatory T cells. Conclusion Up-regulation of IDO is proven to be a mechanism of acquired tolerance in tumors, in which the closely coupled positive feedback system between IDO and reclulatorv T cells may be considered to play an important role.

关键词： indoleamine 2,3-dioxygenase immune tolerance dendritic cells regulatory T cells 1-methyl-tryptophan

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