| Tumour-mediated TRAIL-Receptor expression indicates effective apoptotic depletion of infiltrating CD8+ immune cells in clinical colorectal cancer. | |
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MedLine Citation:
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PMID: 20580220 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Expression of apoptosis-related proteins on tumour cells has been shown in several experimental models to be an efficient mechanism for a counterattack against host anti-tumour immune responses in solid tumours. Here we provide a clinical evidence for such a tumour immune escape mechanism by demonstrating tumour to T cell-directed death receptor signalling (TRAIL/TRAIL-Receptor (TRAIL-R)) in colorectal cancer (CRC). In a series of patients with CRC and completed 5-year follow up, we investigated apoptosis and expression levels of apoptosis-related proteins. Gene and protein profiles in the tumours demonstrated intratumoural upregulated gene expression for Fas, Fas-L, TRAIL, TRAIL-R and TNF-alpha (RT-qPCR). Levels of terminaldeoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labelling (TUNEL)-positive events were positively correlated with TRAIL-R1-expression on tumour infiltrating immune cells. Among the immune cells, preferentially CD8+ T cells were found to express TRAIL-R1 while serial immunostaining in the same patient tumours showed abundant apoptotic (TUNEL-positive) immune cells. In conclusion, our results in tumour samples from CRC patients suggest TRAIL-R1-mediated apoptotic depletion of infiltrating immune cells (CD8+) in response to TRAIL expression by the tumour itself. This supports the notion of an efficient escape from tumour immune response and thus evasion from the attack of activated CD8+ T cells. These findings may enhance our understanding of tumour progression in CRC and might be helpful for the development of TRAIL and its death receptor-based therapy. |
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Authors:
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Martin Grimm; Mia Kim; Andreas Rosenwald; Burkhard H A von Raden; Burkhard von Rahden; Igor Tsaur; Eva Meier; Uwe Heemann; Christoph-Thomas Germer; Martin Gasser; Ana Maria Waaga-Gasser |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-25 |
Journal Detail:
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Title: European journal of cancer (Oxford, England : 1990) Volume: 46 ISSN: 1879-0852 ISO Abbreviation: Eur. J. Cancer Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-04 Completed Date: 2010-12-27 Revised Date: 2011-11-07 |
Medline Journal Info:
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Nlm Unique ID: 9005373 Medline TA: Eur J Cancer Country: England |
Other Details:
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Languages: eng Pagination: 2314-23 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, 97080 Wuerzburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Apoptosis / genetics CD8-Positive T-Lymphocytes / metabolism* Colorectal Neoplasms / genetics, metabolism*, pathology Female Humans In Situ Nick-End Labeling Inhibitor of Apoptosis Proteins / metabolism Interferon-gamma / metabolism Kaplan-Meier Estimate Male Middle Aged Receptors, Death Domain / metabolism Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Inhibitor of Apoptosis Proteins; 0/Receptors, Death Domain; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
Erratum In:
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Eur J Cancer. 2011 Oct;47(15):2373 Note: von Rahden, Burkhard [corrected to von Raden, Burkhard H A] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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