Low expression of chemokine receptor CCR5 in human  colorectal cancer correlates with lymphatic dissemination  and reduced CD8+ T-cell infiltration.
BACKGROUND
Chemokines and their receptors have been proposed to distinctly contribute to tumor growth, dissemination, and local immune escape. The aim of this study was to evaluate the relevance of the chemokine receptor CCR5 expression for the progression of human colorectal cancer.


METHODS
CCR5 expression was assessed by RT-PCR analysis in 103 colorectal cancer patients. Intensity of CCR5 expression was correlated with both tumor and patient characteristics. Infiltration of tumor margins with CD8(+) T cells in the context of CCR5 expression was analyzed by immunohistochemistry in additional 18 colorectal cancer specimens.


RESULTS
Human colorectal cancer revealed variable intensities of CCR5 expression ranging from absent (48/103: 47%), weak (30/103: 29%), intermediate (13/103: 13%), to strong (12/103: 12%). Absent or weak CCR5 expression was significantly associated with advanced UICC stages (P=0.02) and lymphatic metastasis (P=0.05). In addition, CCR5 expression positively correlated with CD8(+) T-cell infiltration in tumor margins (P=0.001).


CONCLUSIONS
In summary, intermediate and strong CCR5 expression was significantly associated with nonmetastatic colorectal cancer and increased CD8(+) T-cell infiltration.
Zimmermann
Tim
T
First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Mainz, Germany.
Moehler
Markus
M
Gockel
Ines
I
Sgourakis
George G
GG
Biesterfeld
Stefan
S
Müller
Michaela
M
Berger
Martin R
MR
Lang
Hauke
H
Galle
Peter R
PR
Schimanski
Carl C
CC
D015415:Biomarkers; D014408:Biomarkers, Tumor; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000276:immunology*; D009367:Neoplasm Staging / Q000379:methods; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D014408:Biomarkers, Tumor; D019713:Receptors, CCR5