Tumour-mediated TRAIL-Receptor expression indicates effective apoptotic depletion of infiltrating CD8+ immune cells in clinical colorectal cancer |
| |
| Authors: | Martin Grimm Mia Kim Andreas Rosenwald Burkhard von Rahden Igor Tsaur Eva Meier Uwe Heemann Christoph-Thomas Germer Martin Gasser Ana Maria Waaga-Gasser |
| |
| Affiliation: | 1. Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, 97080 Wuerzburg, Germany;2. Department of Surgery I, University of Wuerzburg, Wuerzburg, Germany;3. Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany;4. Department of Urology, University of Frankfurt, Frankfurt, Germany;5. Department of Nephrology, University of Munich, Klinikum rechts der Isar, Munich, Germany;1. Stroke Unit, Neurosciences Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal;2. Laboratory of Neuropathology, Neurosciences Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal;3. Department of Nephrology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal;4. Instituto de Medicina Molecular, Lisbon Medical School, Lisbon, Portugal;1. Department of Gastroenterological Surgery, Fukuoka University School of Medicine, Fukuoka, Japan;2. Department of Molecular Pathology, Nara Medical University, Kashihara, Japan;1. Department of Oncology, Catharina Hospital, Eindhoven, The Netherlands;2. Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands;3. Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands;4. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands;1. Department of Surgery, Moores UCSD Cancer Center, University of California San Diego, San Diego, CA;2. OncoFluor, Inc., San Diego, CA;3. AntiCancer, Inc., San Diego, CA |
| |
| Abstract: | 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-α (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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
