The impact of interferon gamma receptor expression on the mechanism of escape from host immune surveillance in hepatocellular carcinoma

被引：71

作者：

Nagao, M ^{[1
]}

Nakajima, Y ^{[1
]}

Kanehiro, H ^{[1
]}

Hisanaga, M ^{[1
]}

Aomatsu, Y ^{[1
]}

Ko, S ^{[1
]}

Tatekawa, Y ^{[1
]}

Ikeda, N ^{[1
]}

Kanokogi, H ^{[1
]}

Urizono, Y ^{[1
]}

Kobayashi, T ^{[1
]}

Shibaji, T ^{[1
]}

Kanamura, T ^{[1
]}

Ogawa, S ^{[1
]}

Nakano, H ^{[1
]}

机构：

[1] Nara Med Univ, Dept Surg 1, Kashihara, Nara 634, Japan

来源：

HEPATOLOGY | 2000年 / 32卷 / 03期

关键词：

D O I：

10.1053/jhep.2000.16470

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 upregulated 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.

引用

页码：491 / 500

页数：10