gms | German Medical Science

126. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

28.04. - 01.05.2009, München

Einfluss des IDO2-Blockers D-1MT auf die IDO-Aktivität humaner Tumoren und dendritischer Zellen

Meeting Abstract

  • S. Löb - Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Tübingen, Deutschland
  • P. Terness - Institut für Immunologie, Abteilung für Transplantationsimmunologie, Heidelberg, Deutschland
  • D. Zieker - Klinik für Allgemeine, Viszeral und Transplantationschirurgie, Tübingen, Deutschland
  • R. Schäfer - Institut für Klinische und Experimentelle Transfusionsmedizin, Tübingen, Deutschland
  • corresponding author B. Brücher - Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Tübingen, Deutschland
  • H.G. Rammensee - Interfakultäres Institut für Zellbiologie, Abteilung für Immunologie, Tübingen, Deutschland
  • A. Königsrainer - Klinik für Allgemeine, Viszeral- und Transplantationschirurgie, Tübingen, Deutschland

Deutsche Gesellschaft für Chirurgie. 126. Kongress der Deutschen Gesellschaft für Chirurgie. München, 28.04.-01.05.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09dgch11664

doi: 10.3205/09dgch187, urn:nbn:de:0183-09dgch1874

Published: April 23, 2009

© 2009 Löb et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Introduction: Clinical phase-I-trials with cancer patients have been started with the aim of inducing tumor immunity by blocking the immunosuppressive action of indoleamine-2,3-dioxygenase (IDO) with the IDO2-inhibitor dextro-1-methyl-tryptophan (D-1MT). In this study we analyzed IDO2- and IDO1-expression in human dendritic cells (DCs) and tumor cells and further investigated the impact of their respective inhibitors, D-1MT and L-1MT on the abrogation of IDO-activity.

Material and methods: Human mDCs, established tumor cells lines, surgically removed human primary gastric-, colon- and renal cell carcinoma specimens were analyzed for IDO1- and IDO2-expression by RT-PCR. siRNA treatment specific for IDO1 was evaluated by qRT-PCR. IDO-activity was measured and quantified by RP-HPLC.

Results: Human primary tumors investigated in this study constitutively expressed various amounts of IDO1 and IDO2, whereas tumor cell lines and DCs needed to be induced by Interfon-gamma (IFN-γ). Transfection with IDO1-specific siRNA blocked IDO1-transcription in cell lines and DCs. IDO2-expression remained unaffected. Tryptophan breakdown was completely restored upon IDO1-siRNA transfection of tumor cell lines and DCs. Addition of L-1MT, but not D-1MT abrogated IDO-activity of tumor cell lines, DCs and freshly isolated colon carcinoma tumor.

Conclusion: Tumor cells and DCs express IDO2, but in a functionally inactive form. Most importantly, D-1MT does not block their IDO-activity. Therefore, L-1MT is the appropriate candidate for inhibiting IDO.

Figure 1 [Fig. 1]