B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression

被引:126
作者
Geng, Lei
Huang, Dongsheng [2 ]
Liu, Junwei [2 ]
Qian, Yigang
Deng, Junfang
Li, Donglin
Hu, Zhenhua
Zhang, Jian [3 ]
Jiang, Guoping
Zheng, Shusen [1 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Minist Publ Hlth,Key Lab Combined Multiorgan Tran, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Sir Run Run Shaw Affiliated Hosp, Dept Gen Surg, Hangzhou 310016, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Anesthesiol, Hangzhou 310003, Zhejiang, Peoples R China
关键词
B7-H1; pancreatic carcinoma; interleukin-10;
D O I
10.1007/s00432-008-0364-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Aberrant tumor cell B7-H1 expression, a member of B7 family that can predominantly stimulate interleukin 10 (IL-10) products, contributed to the tumor immune evasion and tumor progression. This study was designed to investigate the expression of B7-H1 and IL-10 in normal pancreas tissues and pancreatic carcinoma samples, and to evaluate clinical significance of B7-H1 expression in pancreatic carcinoma. Methods First, the B7-H1 and IL-10 expression in 40 pancreatic carcinoma samples and 8 healthy pancreas specimens using reverse transcription-PCR (RT-PCR) and western-blotting was detected. Localization of B7-H1 and IL-10 was confirmed by immunohistochemical (IHC) staining. Next, the association between B7-H1 expression and tumor differentiation and tumor stage was analyzed. Finally, the correlation between tumor-associated B7-H1 and IL-10 was evaluated. Results Pancreatic carcinoma samples demonstrated the up-regulated expression of B7-H1 and IL-10 at mRNA and protein level compared with normal pancreas tissues. IHC staining revealed that B7-H1 and IL-10 was almost localized in tumor cells. Analysis of relationship between B7-H1 and tumor clinicopathological characteristics showed that B7-H1 expression was significantly associated with poor tumor differentiation (P < 0.01) and advanced tumor stage (P < 0.01). Meanwhile, tumor-associated B7-H1 expression was also correlated with IL-10 products (P < 0.01, R-2 = 0.6985, mRNA level; P < 0.01, R-2 = 0.7236, protein level) in tumor cells. Conclusions Our findings for the first time demonstrated up-regulated B7-H1 expression in human pancreatic carcinoma tissues, which might play a role in tumor progression and invasiveness. This expression seemed to be related to the ability of B7-H1 to promoting IL-10 secretion.
引用
收藏
页码:1021 / 1027
页数:7
相关论文
共 21 条
[1]   Mechanisms of interleukin-10-mediated immune suppression [J].
Akdis, CA ;
Blaser, K .
IMMUNOLOGY, 2001, 103 (02) :131-136
[2]   Tumor-associated transforming growth factor-β and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients [J].
Bellone, G ;
Turletti, A ;
Artusio, E ;
Mareschi, K ;
Carbone, A ;
Tibaudi, D ;
Robecchi, A ;
Emanuelli, G ;
Rodeck, U .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (02) :537-547
[3]  
Carter LL, 2002, EUR J IMMUNOL, V32, P634, DOI 10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO
[4]  
2-9
[5]   Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity [J].
Curiel, TJ ;
Wei, S ;
Dong, HD ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Krzysiek, R ;
Knutson, KL ;
Daniel, B ;
Zimmermann, MC ;
David, O ;
Burow, M ;
Gordon, A ;
Dhurandhar, N ;
Myers, L ;
Berggren, R ;
Hemminki, A ;
Alvarez, RD ;
Emilie, D ;
Curiel, DT ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2003, 9 (05) :562-567
[6]  
Dong HD, 1999, NAT MED, V5, P1365
[7]  
Dong HD, 2002, NAT MED, V8, P793, DOI 10.1038/nm730
[8]  
Erdman SE, 2003, CANCER RES, V63, P6042
[9]   B7-H1 expression is upregulated in peripheral blood CD14+monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levels [J].
Geng, L. ;
Jiang, G. ;
Fang, Y. ;
Dong, S. ;
Xie, H. ;
Chen, Y. ;
Shen, M. ;
Zheng, S. .
JOURNAL OF VIRAL HEPATITIS, 2006, 13 (11) :725-733
[10]   Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade [J].
Iwai, Y ;
Ishida, M ;
Tanaka, Y ;
Okazaki, T ;
Honjo, T ;
Minato, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (19) :12293-12297