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Decreased expression of B7 costimulatory molecules and major histocompatibility complex class-I in human hepatocellular carcinoma
Authors:Fujiwara Keishi  Higashi Toshihiro  Nouso Kazuhiro  Nakatsukasa Harushige  Kobayashi Yoshiyuki  Uemura Masayuki  Nakamura Shin-Ichiro  Sato Shuichiro  Hanafusa Tadashi  Yumoto Yasuhiro  Naito Ichiro  Shiratori Yasushi
Institution:Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Abstract:BACKGROUND AND AIM: We analyzed the expression of antigen-processing and antigen-presenting molecules in surgically resected fresh samples of human hepatocellular carcinoma (HCC) tissue to elucidate a mechanism of immune escape. We also examined the expression of interleukin (IL)-10 protein, which might act to downregulate expression of antigen-processing and antigen-presenting molecules. METHODS: Twenty-eight HCC samples obtained by surgical resection were analyzed for the expression of beta2-microglobulin, heat-shock protein (HSP)-70, human leukocyte antigen (HLA) class-I, CD80 (B7-1), CD86 (B7-2) and IL-10 by immunostaining. RESULTS: Beta2-microglobulin and HSP-70 were preserved in all samples. In contrast, the expression of HLA class-I molecules was significantly reduced according to lowering in the histological grading of tumor differentiation (P = 0.024). Furthermore, B7-1 and B7-2 expression was reduced in tumor cells compared with corresponding areas of liver tissue without malignant involvement irrespective of the histological grading of tumors (21% and 36%, respectively). Although IL-10 protein was expressed in 54% of HCC, no relationship between the expression of IL-10 and downregulation of B7-1, B7-2, and HLA class-I was evident. CONCLUSION: These findings suggest the potential role of B7 co-stimulatory molecules and HLA class-I molecules in facilitating HCC escape from immune surveillance without the involvement of IL-10.
Keywords:immune tolerance  liver  neoplasm  tumor escape
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