The alteration of fas receptor and ligand system in hepatocellular carcinomas: How do hepatoma cells escape from the host immune surveillance in vivo?

Escape from the immune surveillance may play an important role in tumor outgrowth and metastasis. Alteration of the Fas receptor (Fas)/ligand (FasL) system including soluble forms is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. However, less attentio...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 1999-08, Vol.30 (2), p.413-421
Main Authors: Nagao, Mitsuo, Nakajima, Yoshiyuki, Hisanaga, Michiyoshi, Kayagaki, Nobuhiko, Kanehiro, Hiromichi, Aomatsu, Yukio, Ko, Saiho, Yagita, Hideo, Yamada, Takatsugu, Okumura, Ko, Nakano, Hiroshige
Format: Article
Language:English
Subjects:
Adult
Aged
Apoptosis
Biological and medical sciences
Carcinoma, Hepatocellular - immunology
Carcinoma, Hepatocellular - mortality
Carcinoma, Hepatocellular - pathology
Digestive system
Fas Ligand Protein
fas Receptor - analysis
Female
Humans
Immunohistochemistry
Investigative techniques, diagnostic techniques (general aspects)
Liver Neoplasms - immunology
Liver Neoplasms - mortality
Liver Neoplasms - pathology
Male
Medical sciences
Membrane Glycoproteins - analysis
Middle Aged
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Survival Rate
Tumor Suppressor Protein p53 - analysis
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Summary:Escape from the immune surveillance may play an important role in tumor outgrowth and metastasis. Alteration of the Fas receptor (Fas)/ligand (FasL) system including soluble forms is regarded as one of the mechanisms preventing the immune system from rejecting the tumor cells. However, less attention has been paid to the role of Fas/FasL interaction in vivo. Therefore, we investigated the expression of Fas and FasL by immunohistochemistry and reverse‐transcription polymerase chain reaction (RT‐PCR) and measured the serum levels of soluble Fas (sFas) and FasL (sFasL) in 44 patients with hepatocellular carcinoma (HCC). In the noncancerous liver tissues, Fas expression was up‐regulated in most cases, and FasL expression was detected in 6 cases. In Fas‐positive HCC cases (n = 15), the intrahepatic metastatic foci was less (P = .037), apoptosis of tumor cells was more (P = .004), the disease‐free survival rate was higher (P = .004), and p53‐positive cases were less (P = .003), compared with Fas‐negative cases. The sFas and sFasL levels in HCC patients were significantly higher and lower than those in controls, respectively. RT‐PCR and immunohistochemistry revealed generation of sFas in the hepatocytes and tumor‐infiltrating mononuclear cells rather than in hepatoma cells. Accordingly, hepatoma cells may eliminate Fas expression on themselves and let the hepatocytes and infiltrating mononuclear cells generate sFas to escape from the immune system and to produce metastasis. FasL might contribute to malignant transformation in some circumstances, because hepatocytes in the pericancerous pseudolobules expressed FasL.
ISSN:0270-9139
1527-3350
DOI:10.1002/hep.510300237