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Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor‐infiltrating lymphocytes
Author(s) -
Hirano Seitaro,
Iwashita Yukio,
Sasaki Atsushi,
Kai Seiichiro,
Ohta Masayuki,
Kitano Seigo
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04551.x
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , chemokine , messenger rna , microbiology and biotechnology , cd8 , immunohistochemistry , interferon , biology , medicine , immunology , antigen , immune system , gene , biochemistry
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‐γ (Mig), and interferon‐γ 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 mm 2 . 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‐γ. 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‐γ, such as Mig and IP‐10, may promote lymphocyte recruitment to HCC and may thus play important roles in cancer immunology.