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The Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular Carcinoma

2000; Lippincott Williams & Wilkins; Volume: 32; Issue: 3 Linguagem: Inglês

10.1053/jhep.2000.16470

1527-3350

Mitsuo Nagao, Yoshiyuki Nakajima, Hiromichi Kanehiro, Michiyoshi Hisanaga, Yukio Aomatsu, Saiho Ko, Yukihiro Tatekawa, Naoya Ikeda, Hideki Kanokogi, Yasuyuki Urizono, Tsunehiro Kobayashi, Takamune Shibaji, Tetsuhiro Kanamura, Sanehito Ogawa, Hiroshige Nakano,

Immune Cell Function and Interaction

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.