title: The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: First Department of Surgery, Nara Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: Y
authors.initials: Y
authors.lastname: Nakajima
authors.forename: H
authors.initials: H
authors.lastname: Kanehiro
authors.forename: M
authors.initials: M
authors.lastname: Hisanaga
authors.forename: Y
authors.initials: Y
authors.lastname: Aomatsu
authors.forename: S
authors.initials: S
authors.lastname: Ko
authors.forename: Y
authors.initials: Y
authors.lastname: Tatekawa
authors.forename: N
authors.initials: N
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Kanokogi
authors.forename: Y
authors.initials: Y
authors.lastname: Urizono
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Shibaji
authors.forename: T
authors.initials: T
authors.lastname: Kanamura
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Nakano
mesh_terms: D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D000096743:Interferon gamma Receptor
chemical_list: D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor