Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes

Abstract

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.