Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wobser, M; Voigt, H; Houben, R; Eggert, AO; Freiwald, M; Kaemmerer, U; Kaempgen, E; Schrama, D; Becker, JC.
Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression.
Cancer Immunol Immunother. 2007; 56(7):1017-1024
Doi: 10.1007/s00262-006-0256-1
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Co-Autor*innen der Med Uni Graz
- Schrama David
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- Abstract:
- BACKGROUND: Recent reports have demonstrated that the enzyme indoleamine 2,3-dioxygenase (IDO) is upregulated in human dendritic cells (DCs) upon in vitro maturation. IDO is supposed to convey immunosuppressive effects by degrading the essential amino acid tryptophan, thereby downregulating T-cell functions. Hence, we evaluated IDO expression in DC preparations used for therapeutic DC vaccination and its in vivo effects. PATIENTS, METHODS AND RESULTS: IDO expression was detected by real-time-PCR in a series of human clinical grade DCs (n = 28) prior to vaccination of advanced melanoma patients (n = 11). These analyses revealed an intra- and interpersonal variation in IDO mRNA levels. IDO was strongly upregulated in human DCs on RNA and on protein level upon in vitro maturation by Interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and Prostaglandin E2 (PGE2) over a time course of 24 h. The enzymatic activity of induced IDO was demonstrated by measuring tryptophan degradation. Moreover, in biopsies obtained 24 h after application of the DC vaccine a prominent infiltrate of IDO-positive cells was observed by immunohistochemistry. The inflammatory infiltrate of these sites stained positive for the transcription factor Forkhead box P3 (FoxP3), suggesting an IDO-mediated induction of regulatory T-cells. All analysed melanoma patients (n = 11) receiving DC based immunotherapy exhibited rapid disease progression with a short overall survival due to advanced tumour stage. CONCLUSION: The presented observations suggest a potential clinical relevance of IDO expression in DC-based therapeutic vaccines via the attraction or induction of FoxP3(+) T-cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Animals -
- Blotting, Western -
- Cancer Vaccines - immunology Cancer Vaccines - metabolism Cancer Vaccines - therapeutic use
- Dendritic Cells - enzymology Dendritic Cells - immunology
- Female -
- Forkhead Transcription Factors - metabolism
- Humans -
- Immunohistochemistry -
- Immunotherapy -
- Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
- Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism
- Male -
- Melanoma - immunology Melanoma - therapy
- Middle Aged -
- RNA, Messenger - analysis
- Reverse Transcriptase Polymerase Chain Reaction -
- Tryptophan - metabolism
- Find related publications in this database (Keywords)
- indoleamine 2
- 3-dioxygenase (IDO)
- dendritic cell (DC)
- immunotherapy