Title: The Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular Carcinoma
Abstract: HepatologyVolume 32, Issue 3 p. 491-500 Original ArticleFree Access The Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular Carcinoma Mitsuo Nagao M.D., Corresponding Author Mitsuo Nagao M.D. From the First Department of Surgery, Nara Medical University, Nara, JapanFirst Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara 634, Japan. Fax: (81) 7442-4-6866.===Search for more papers by this authorYoshiyuki Nakajima, Yoshiyuki Nakajima From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHiromichi Kanehiro, Hiromichi Kanehiro From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorMichiyoshi Hisanaga, Michiyoshi Hisanaga From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYukio Aomatsu, Yukio Aomatsu From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorSaiho Ko, Saiho Ko From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYukihiro Tatekawa, Yukihiro Tatekawa From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorNaoya Ikeda, Naoya Ikeda From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHideki Kanokogi, Hideki Kanokogi From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYasuyuki Urizono, Yasuyuki Urizono From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTsunehiro Kobayashi, Tsunehiro Kobayashi From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTakamune Shibaji, Takamune Shibaji From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTetsuhiro Kanamura, Tetsuhiro Kanamura From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorSanehito Ogawa, Sanehito Ogawa From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHiroshige Nakano, Hiroshige Nakano From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this author Mitsuo Nagao M.D., Corresponding Author Mitsuo Nagao M.D. From the First Department of Surgery, Nara Medical University, Nara, JapanFirst Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara City, Nara 634, Japan. Fax: (81) 7442-4-6866.===Search for more papers by this authorYoshiyuki Nakajima, Yoshiyuki Nakajima From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHiromichi Kanehiro, Hiromichi Kanehiro From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorMichiyoshi Hisanaga, Michiyoshi Hisanaga From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYukio Aomatsu, Yukio Aomatsu From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorSaiho Ko, Saiho Ko From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYukihiro Tatekawa, Yukihiro Tatekawa From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorNaoya Ikeda, Naoya Ikeda From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHideki Kanokogi, Hideki Kanokogi From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorYasuyuki Urizono, Yasuyuki Urizono From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTsunehiro Kobayashi, Tsunehiro Kobayashi From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTakamune Shibaji, Takamune Shibaji From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorTetsuhiro Kanamura, Tetsuhiro Kanamura From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorSanehito Ogawa, Sanehito Ogawa From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this authorHiroshige Nakano, Hiroshige Nakano From the First Department of Surgery, Nara Medical University, Nara, JapanSearch for more papers by this author First published: 30 December 2003 https://doi.org/10.1053/jhep.2000.16470Citations: 46AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Interferon gamma (IFN-γ) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-γ 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-γ receptor (IFN-γ-R). Although hepatocytes in normal liver express weak or no IFN-γ-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-γ-R α-chain knock-out mice revealed the actions of IFN-γ 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-γ to evade host immune surveillance. We examined the expression of IFN-γ-R and IFN-γ–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-γ-R expression on the cell surface was up-regulated in 27 cases. In IFN-γ-R–negative cases (n = 15), tumor size was larger (P = .032), serum α-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-γ-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-γ-R and the expression of Fas and MHC implies that the loss of IFN-γ-R might contribute to the mechanism of escape from host immune rejection in HCC. REFERENCES 1 Munoz N, Lincell A. Epidemiology of primary liver cancer. 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