1.Costimulatory molecule B7-H1 on the immune escape of bladder cancer and its clinical significance.
Yonghua, WANG ; Qianyuan, ZHUANG ; Siwei, ZHOU ; Zhiquan, HU ; Ruzhu, LAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(1):77-9
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were constructed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P<0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.
Antigens, CD/genetics
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Antigens, CD/*metabolism
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Antigens, CD80/genetics
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Antigens, CD80/*metabolism
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Prognosis
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Tumor Escape/*genetics
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Urinary Bladder Neoplasms/*immunology
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Urinary Bladder Neoplasms/metabolism
2.Suppression of Tumor Formation and Induction of Natural Killer Cell Activity in BALB/c Nude Mice by Human B7-1 (CD80) Gene Transfer Subcutaneously Injected with Human Hepatocellular Carcinoma Cells (Huh-7).
Seung Kew YOON ; Tai Gyu KIM ; Hyun Il CHO ; Bong Soo LEE ; Se Hyun CHO ; Nam Ik HAN ; Young Sok LEE ; Jeong Won JANG ; Kyu Won CHUNG ; Hee Sik SUN ; Boo Sung KIM
The Korean Journal of Hepatology 2003;9(2):124-134
BACKGROUND/AIMS: Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. METHODS: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2 X 10(6) Huh-7/hB7-1 cells, while the other 7 were injected with 2 X 10(6) Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-gamma was performed at 1 and 2 weeks after inoculation. RESULTS: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-gamma was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. CONCLUSIONS: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.
Animals
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Antigens, CD80/*genetics
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Cytotoxicity, Immunologic
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Gene Transfer Techniques
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Humans
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Interferon-gamma/metabolism
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Killer Cells, Natural/*immunology
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Liver Neoplasms, Experimental/genetics/*immunology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Transplantation