The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma
| Autor: | Michiyoshi Hisanaga, Hiromichi Kanehiro, Sanehito Ogawa, Mitsuo Nagao, Yasuyuki Urizono, Saiho Ko, Hideki Kanokogi, Yukihiro Tatekawa, Tsunehiro Kobayashi, Yoshiyuki Nakajima, Hiroshige Nakano, Naoya Ikeda, Tetsuhiro Kanamura, Takamune Shibaji, Yukio Aomatsu |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Carcinoma Hepatocellular medicine.medical_treatment Blotting Western Host Defense Mechanism Apoptosis Biology Chronic liver disease Major histocompatibility complex Interferon-gamma Immune system Lymphocytes Tumor-Infiltrating Interferon-gamma receptor medicine Humans Interferon gamma RNA Messenger Aged Receptors Interferon Hepatology Histocompatibility Antigens Class I Liver Neoplasms Middle Aged medicine.disease Cytokine Ki-67 Antigen Gene Expression Regulation Immunology biology.protein Female Signal transduction medicine.drug |
| Zdroj: | Hepatology (Baltimore, Md.). 32(3) |
| ISSN: | 0270-9139 |
| Popis: | Interferon gamma (IFN-gamma) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-gamma exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-gamma receptor (IFN-gamma-R). Although hepatocytes in normal liver express weak or no IFN-gamma-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-gamma-R alpha-chain knock-out mice revealed the actions of IFN-gamma on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-gamma to evade host immune surveillance. We examined the expression of IFN-gamma-R and IFN-gamma-inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-gamma-R expression on the cell surface was up-regulated in 27 cases. In IFN-gamma-R-negative cases (n = 15), tumor size was larger (P =.032), serum alpha-fetoprotein (AFP) level was higher (P =.001), intrahepatic and extrahepatic metastasis was more common (P =.044 and.013, respectively), and Ki-67 labeling index (LI) was higher (P =.041), compared with IFN-gamma-R-positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-gamma-R and the expression of Fas and MHC implies that the loss of IFN-gamma-R might contribute to the mechanism of escape from host immune rejection in HCC. |
| Databáze: | OpenAIRE |
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