Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes.
BACKGROUND
The infiltration of lymphocytes in tumor tissue has been associated with a good prognosis for patients with hepatocellular carcinoma (HCC). The purpose of the present study was to estimate the correlation between mRNA expression of chemokines and tumor-infiltrating lymphocytes in HCC.


METHODS
A total of 44 HCC were examined. Immunohistochemical staining was performed using antibodies to CD4, CD8, CD68, and L-26. The mRNA expression of each chemokine was investigated: regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78 (ENA78), interferon-inducible protein-10 (IP-10), monokine induced by interferon-gamma (Mig), and interferon-gamma in HCC were quantified via a real-time polymerase chain reaction assay. Chemokine proteins of Mig and IP-10 were examined by immunohistochemistry.


RESULTS
The mean number of infiltrating lymphocytes in HCC was 136.9 +/- 32.9/0.25 mm2. Of these infiltrating lymphocytes, CD8-positive T lymphocytes were those predominantly seen around the tumor cells. The mean mRNA expression (copies/10(3) glyceraldehyde-3-phosphate dehydrogenase [GAPDH] mRNA) of the following chemokines was determined to be follows: 3.0 +/- 1.9 copies/10(3) GAPDH mRNA, RANTES; 9.2 +/- 4.9 copies/10(3) GAPDH mRNA, IL-8; 44.6 +/- 24.4 copies/10(3) GAPDH mRNA, ENA78; 215.7 +/- 93.9 copies/10(3) GAPDH mRNA, IP-10; 77.3 +/- 38.5 copies/10(3) GAPDH mRNA, Mig; and 1.7 +/- 0.4 copies/10(3) GAPDH mRNA, interferon-gamma. Significant close correlations were observed between the number of infiltrating lymphocytes in these HCC and the expression of Mig and IP-10 mRNA. In the immunostaining, expression of Mig and IP-10 proteins was found only in the HCC cells in the high-infiltration group.


CONCLUSIONS
Some chemokines induced by interferon-gamma, such as Mig and IP-10, may promote lymphocyte recruitment to HCC and may thus play important roles in cancer immunology.
Hirano
Seitaro
S
Department of Surgery I, Oita University Faculty of Medicine, Yufu, Oita, Japan. ohirano@med.oita-u.ac.jp
Iwashita
Yukio
Y
Sasaki
Atsushi
A
Kai
Seiichiro
S
Ohta
Masayuki
M
Kitano
Seigo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018946:Chemokine CCL5 / Q000235:genetics; D054357:Chemokine CXCL10; D054365:Chemokine CXCL5; D054370:Chemokine CXCL9; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C114753:CXCL10 protein, human; C486263:CXCL5 protein, human; C080810:CXCL9 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054365:Chemokine CXCL5; D054370:Chemokine CXCL9; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8; D012333:RNA, Messenger; D007371:Interferon-gamma