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
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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“In preclinical models, heightened activity of the Trp-Kyn-AhR pathway has been linked to impairment of antitumor immunity and tumor growth (16,17).”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [17]
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Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0016-5 · Cited by 1,586
Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways
Hakim, M., Broza, Y. Y., Barash, O., Peled, N., Phillips, M., Amann, A., & Haick, H. (2012) · Chemical Reviews · doi:10.1021/cr300174a · Cited by 953
Labadie, B. W., Bao, R., & Luke, J. J. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2882 · Cited by 413
Beatty, G. L., O'Dwyer, P. J., Clark, J., Shi, J. G., Bowman, K. J., Scherle, P. A., Newton, R. C., Schaub, R., Maleski, J., Leopold, L., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2272 · Cited by 314
The therapeutic potential of targeting tryptophan catabolism in cancer
Opitz, C. A., Somarribas Patterson, L. F., Mohapatra, S. R., Dewi, D. L., Sadik, A., Platten, M., & Trump, S. (2020) · British Journal of Cancer · doi:10.1038/s41416-019-0664-6 · Cited by 300
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
- Venue
- Clinical Cancer Research
- Published
- 2006-02-15
- Volume
- 12
- Issue
- 4
- Pages
- 1144-1151
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- 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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