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肝内胆管癌细胞上的B7-H1与肿瘤浸润性T细胞上的PD-1相互作用作为免疫逃逸机制。

Interaction of B7-H1 on intrahepatic cholangiocarcinoma cells with PD-1 on tumor-infiltrating T cells as a mechanism of immune evasion.

作者信息

Ye Yufu, Zhou Lin, Xie Xiaojun, Jiang Guoping, Xie Haiyang, Zheng Shusen

机构信息

Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

出版信息

J Surg Oncol. 2009 Nov 1;100(6):500-4. doi: 10.1002/jso.21376.

DOI:10.1002/jso.21376
PMID:19697355
Abstract

BACKGROUND AND OBJECTIVES

The B7-H1/PD-1 pathway has recently been found to contribute to immune evasion of cancer cells from host immune system. This study aimed to investigate the expression of B7-H1 and its receptor PD-1 and to explore their significance in the progression of intraheptic cholangiocarcinoma (ICC).

METHODS

Thirty-one surgically resected ICC tissues and the corresponding cancer adjacent tissues were enrolled from 2006 to 2007. Immunohistochemical studies were performed with antibody of B7-H1, PD-1, CD8, and CD4. Apoptosis status of tumor-infiltrating lymphocytes (TILs) was detected by TUNEL assay.

RESULTS

Expression of B7-H1 and PD-1 was found to be up-regulated in ICC tissues compared with the cancer adjacent tissues. Tumor-related B7-H1 expression was significantly correlated with both tumor differentiation and pTNM stage and was inversely correlated with CD8+ TILs but not CD4+ TILs. TILs in primary carcinoma showed a high level of apoptosis.

CONCLUSION

B7-H1/PD-1 pathway may be linked to malignant potential of ICC and contribute to tumor immune evasion by promoting CD8+ TILs apoptosis. Thus, this pathway may indeed be a potential therapeutic target in the treatment of this disease.

摘要

背景与目的

最近发现B7-H1/PD-1通路有助于癌细胞逃避宿主免疫系统的免疫监视。本研究旨在探讨B7-H1及其受体PD-1的表达情况,并探讨它们在肝内胆管癌(ICC)进展中的意义。

方法

选取2006年至2007年间手术切除的31例ICC组织及其相应的癌旁组织。采用B7-H1、PD-1、CD8和CD4抗体进行免疫组织化学研究。通过TUNEL法检测肿瘤浸润淋巴细胞(TILs)的凋亡状态。

结果

与癌旁组织相比,ICC组织中B7-H1和PD-1的表达上调。肿瘤相关的B7-H1表达与肿瘤分化和pTNM分期显著相关,与CD8+TILs呈负相关,与CD4+TILs无相关性。原发性癌中的TILs显示出高水平的凋亡。

结论

B7-H1/PD-1通路可能与ICC的恶性潜能相关,并通过促进CD8+TILs凋亡导致肿瘤免疫逃逸。因此,该通路确实可能是治疗这种疾病的潜在治疗靶点。

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