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Cited by 614Cancer Immunotherapy and BiomarkersImmune cells in cancerImmunotherapy and Immune Responses

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells

Brandacher, Gerald, Perathoner, Alexander, Ladurner, Ruth, Schneeberger, Stefan, Obrist, Peter, Winkler, Christiana, Werner, Ernst R, Werner-Felmayer, Gabriele, Weiss, Helmut G, G√∂bel, Georg, Margreiter, Raimund, K√∂nigsrainer, Alfred, Fuchs, Dietmar, Amberger, Albert·2006·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-05-1966
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Abstract

PURPOSE: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) on this phenomenon. EXPERIMENTAL DESIGN: Expression of IDO was analyzed in colorectal cancer cell lines by reverse transcription-PCR and functional enzyme activity was assessed by high-pressure liquid chromatography. Semiquantitative immunohistochemistry was used to evaluate IDO expression in the tissue samples of 143 patients with colorectal carcinoma, and was then correlated with the number of tumor-infiltrating T cells and clinical variables. RESULTS: In vitro IDO expression and functional enzyme activity in colorectal cancer cells was found to be strictly dependent on IFN-gamma stimulation. Immunohistochemical scores revealed IDO-high expression in 56 of 143 (39.2%) tumor specimens, whereas 87 of 143 (60.8%) cases showed low IDO expression levels. IDO-high expression was associated with a significant reduction of CD3+ infiltrating T cells (46.02 +/- 7.25) as compared with tissue samples expressing low IDO (19.42 +/- 2.50; P = 0.0003). Furthermore, IDO-high immunoreactivity significantly correlated with the frequency of liver metastases (P = 0.003). Kaplan-Meier analysis showed the crossing of survival curves at 45 months. By multivariate Cox's analysis, IDO-high expression emerged as an independent prognostic variable (<45 months, P = 0.006; >45 months, P = 0.04). CONCLUSION: IDO-high expression by colorectal tumor cells enables certain cancer subsets to initially avoid immune attack and defeat the invasion of T cells via local tryptophan depletion and the production of proapoptotic tryptophan catabolites. Thus, IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer.

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Crossref · 10.1158/1078-0432.ccr-05-1966

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Metadata

Authors
Brandacher, G., Perathoner, A., Ladurner, R., Schneeberger, S., Obrist, P., Winkler, C., Werner, E. R., Werner-Felmayer, G., Weiss, H. G., Göbel, G., Margreiter, R., Königsrainer, A., Fuchs, D., & Amberger, A.
Affiliations
  • Innsbruck Medical University (AT)
  • Johannes Kepler University of Linz (AT)
  • Department of General and Transplant Surgery, Innsbruck Medical University, Austria. gerald.brandacher@uibk.ac.at
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2006-02-15
Volume
12
Issue
4
Pages
1144-1151
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-05-1966
OpenAlex
W2127903252
Cited by
614
References
30
Citations by year
2026: 8 · 2025: 20 · 2024: 29 · 2023: 31 · 2022: 34 · 2021: 45 · 2020: 41 · 2019: 45 · 2018: 42 · 2017: 36 · 2016: 30 · 2015: 35 · 2014: 21 · 2013: 24 · 2012: 27
FWCI
14.39
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
indoleamine 2,3-dioxygenase, colorectal cancer, tumor-infiltrating T cells, tumor microenvironment, immunosuppression, tryptophan catabolism, liver metastasis, prognostic factors, interferon-gamma, overall survival, CD3+ T cells
MeSH terms
Female, Humans, Immunohistochemistry, Interferon-gamma, Liver Neoplasms, Male, Middle Aged, Prognosis, Retrospective Studies, T-Lymphocytes, Colorectal Neoplasms, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Survival Analysis, CD3 Complex, Disease Progression, Caco-2 Cells, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Indoleamine-Pyrrole 2,3,-Dioxygenase

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