Decreased expression of B7 costimulatory molecules and major histocompatibility complex class-I in human hepatocellular carcinoma.
OBJECTIVE
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.


CONCLUSIONS
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.
Fujiwara
Keishi
K
Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Higashi
Toshihiro
T
Nouso
Kazuhiro
K
Nakatsukasa
Harushige
H
Kobayashi
Yoshiyuki
Y
Uemura
Masayuki
M
Nakamura
Shin-Ichiro
S
Sato
Shuichiro
S
Hanafusa
Tadashi
T
Yumoto
Yasuhiro
Y
Naito
Ichiro
I
Shiratori
Yasushi
Y
D000368:Aged; D018122:B7-1 Antigen / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000276:immunology
D018122:B7-1 Antigen; D018840:HSP70 Heat-Shock Proteins; D001613:beta 2-Microglobulin; D016753:Interleukin-10