PMID- 20580220
OWN - NLM
STAT- MEDLINE
DCOM- 20101227
LR  - 20111107
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 46
IP  - 12
DP  - 2010 Aug
TI  - Tumour-mediated TRAIL-Receptor expression indicates effective apoptotic depletion 
      of infiltrating CD8+ immune cells in clinical colorectal cancer.
PG  - 2314-23
LID - 10.1016/j.ejca.2010.05.025 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
FAU - Grimm, Martin
AU  - Grimm M
AD  - Department of Surgery I, Molecular Oncology and Immunology, University of 
      Wuerzburg, 97080 Wuerzburg, Germany.
FAU - Kim, Mia
AU  - Kim M
FAU - Rosenwald, Andreas
AU  - Rosenwald A
FAU - von Raden, Burkhard H A
AU  - von Raden BH
FAU - Tsaur, Igor
AU  - Tsaur I
FAU - Meier, Eva
AU  - Meier E
FAU - Heemann, Uwe
AU  - Heemann U
FAU - Germer, Christoph-Thomas
AU  - Germer CT
FAU - Gasser, Martin
AU  - Gasser M
FAU - Waaga-Gasser, Ana Maria
AU  - Waaga-Gasser AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100625
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Receptors, Death Domain)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
EIN - Eur J Cancer. 2011 Oct;47(15):2373. von Rahden, Burkhard [corrected to von Raden, 
      Burkhard H A]
MH  - Adult
MH  - Aged
MH  - Apoptosis/genetics
MH  - CD8-Positive T-Lymphocytes/*metabolism
MH  - Colorectal Neoplasms/genetics/*metabolism/pathology
MH  - Female
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Inhibitor of Apoptosis Proteins/metabolism
MH  - Interferon-gamma/metabolism
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Receptors, Death Domain/metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism
MH  - Up-Regulation
EDAT- 2010/06/29 06:00
MHDA- 2010/12/28 06:00
CRDT- 2010/06/29 06:00
PHST- 2009/12/09 00:00 [received]
PHST- 2010/05/19 00:00 [revised]
PHST- 2010/05/24 00:00 [accepted]
PHST- 2010/06/29 06:00 [entrez]
PHST- 2010/06/29 06:00 [pubmed]
PHST- 2010/12/28 06:00 [medline]
AID - S0959-8049(10)00449-1 [pii]
AID - 10.1016/j.ejca.2010.05.025 [doi]
PST - ppublish
SO  - Eur J Cancer. 2010 Aug;46(12):2314-23. doi: 10.1016/j.ejca.2010.05.025. Epub 2010 
      Jun 25.