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

被引:51
作者
Fujiwara, K
Higashi, T
Nouso, K
Nakatsukasa, H
Kobayashi, Y
Uemura, M
Nakamura, SI
Sato, S
Hanafusa, T
Yumoto, Y
Naito, I
Shiratori, Y
机构
[1] Okayama Univ, Grad Sch Med & Dent, Dept Med & Med Sci, Okayama 7008558, Japan
[2] Okayama Univ, Okayama Citizens Hosp, Okayama 7008558, Japan
[3] Okayama Univ, Isotope Ctr, Okayama 7008558, Japan
[4] Shigei Med Res Inst, Okayama, Japan
关键词
immune tolerance; liver; neoplasm; tumor escape;
D O I
10.1111/j.1440-1746.2004.03467.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. (C) 2004 Blackwell Publishing Asia Pty Ltd.
引用
收藏
页码:1121 / 1127
页数:7
相关论文
共 41 条
[21]  
2-T
[22]   INTERLEUKIN-10 PRETREATMENT PROTECTS TARGET-CELLS FROM TUMOR-SPECIFIC AND ALLO-SPECIFIC CYTOTOXIC T-CELLS AND DOWN-REGULATES HLA CLASS-I EXPRESSION [J].
MATSUDA, M ;
SALAZAR, F ;
PETERSSON, M ;
MASUCCI, G ;
HANSSON, J ;
PISA, P ;
ZHANG, QJ ;
MASUCCI, MG ;
KIESSLING, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (06) :2371-2376
[23]   CONSTRUCTION, PURIFICATION, AND FUNCTIONAL INCORPORATION ON TUMOR-CELLS OF GLYCOLIPID-ANCHORED HUMAN B7-1 (CD80) [J].
MCHUGH, RS ;
AHMED, SN ;
WANG, YC ;
SELL, KW ;
SELVARAJ, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :8059-8063
[24]  
Miyagawa S, 1996, HEPATOLOGY, V24, P307
[25]  
Moro M, 1999, CANCER RES, V59, P2650
[26]   HEPATOCELLULAR-CARCINOMA - RECENT PROGRESS [J].
OKUDA, K .
HEPATOLOGY, 1992, 15 (05) :948-963
[27]   HLA EXPRESSION IN HUMAN HEPATOCELLULAR-CARCINOMA [J].
PATERSON, AC ;
SCIOT, R ;
KEW, MC ;
CALLEA, F ;
DUSHEIKO, GM ;
DESMET, VJ .
BRITISH JOURNAL OF CANCER, 1988, 57 (04) :369-373
[28]  
SalazarOnfray F, 1997, J IMMUNOL, V159, P3195
[29]   The effect of human β2-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant -: Implications for peptide-based vaccines [J].
Shields, MJ ;
Kubota, R ;
Hodgson, W ;
Jacobson, S ;
Biddison, WE ;
Ribaudo, RK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) :28010-28018
[30]  
Stearns ME, 1998, CLIN CANCER RES, V4, P2257