Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) is a rapidly progressive malignancy. Chemokine receptors are important mediators of lymphocyte migration in cancer. This study evaluated expression of chemokine receptors on lymphocytes of HCC patients.


METHODS
Chemokine receptor expression on peripheral blood lymphocytes (PBL) was determined by flow cytometry and RT-PCR. Tumor infiltrating lymphocytes (TIL) and adjacent nontumor liver infiltrating lymphocytes (NIL) were also studied.


RESULTS
The expressions of CCR5, CCR6, and CXCR3 on PBL were significantly reduced in HCC patients compared with normal controls, which occurred concurrently with increased expression of the chemokine receptors in TIL and NIL. Reduced expression of CXCR3 on PBL correlated with large tumor size and advanced tumor stage. The reduced chemokine receptor expression was consistent with the reduced mRNA levels and intracellular protein levels in PBL. HCC patients exhibited lower proportions of CD4(+) and CD8(+) T cells with CCR5, CCR6, and CXCR3 expression on PBL, which occurred concurrently with the increased expression of these chemokine receptors on TIL and NIL. The reduced CCR6 and CXCR3 expression on PBL correlated with the reduced memory phenotype in circulation and increased memory phenotype in liver. Furthermore, CCR5-expressing memory T cells were increased in liver compartment compared with circulation.


CONCLUSIONS
This study demonstrated that reduced chemokine receptor expression on PBL was concurrent with increased chemokine receptor expression on both TIL and NIL in HCC. The results demonstrated the role of chemokine receptors in recruitment of lymphocytes from peripheral blood to HCC. The findings have important implications in understanding of immunopathogenesis of HCC.
Liu
Yuqing
Y
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, ROC.
Poon
Ronnie T
RT
Feng
Xiaoqin
X
Yu
Wan Ching
WC
Luk
John M
JM
Fan
Sheung Tat
ST
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000235:genetics; D018956:CD5 Antigens / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D017252:CD3 Complex; D018956:CD5 Antigens; D005819:Genetic Markers; D019713:Receptors, CCR5; D019707:Receptors, Chemokine