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非小细胞肺癌细胞上B7-H1的表达及其与肿瘤浸润淋巴细胞及其PD-1表达的关系。

B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

作者信息

Konishi Jun, Yamazaki Koichi, Azuma Miyuki, Kinoshita Ichiro, Dosaka-Akita Hirotoshi, Nishimura Masaharu

机构信息

First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Clin Cancer Res. 2004 Aug 1;10(15):5094-100. doi: 10.1158/1078-0432.CCR-04-0428.

Abstract

PURPOSE

B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs.

EXPERIMENTAL DESIGN

The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically.

RESULTS

Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02).

CONCLUSIONS

The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.

摘要

目的

B7-H1/程序性死亡配体1(B7-H1)和B7-DC/程序性死亡配体2(B7-DC)是受体程序性死亡蛋白1(PD-1)的配体,已知其对T细胞活化具有负性调节作用。在本研究中,我们调查了非小细胞肺癌肿瘤标本中B7-H1和B7-DC的表达情况,及其与临床病理变量和术后生存的关系。此外,我们检测了肿瘤细胞上B7-H1表达与肿瘤浸润淋巴细胞(TILs)数量或TILs上PD-1表达之间的相关性。

实验设计

采用免疫组织化学方法评估52例手术切除的非小细胞肺癌标本中B7-H1和B7-DC的表达。

结果

在所有非小细胞肺癌肿瘤标本中均局灶性观察到B7-H1和B7-DC的表达。未发现B7-H1或B7-DC的表达与临床病理变量或术后生存之间存在相关性。然而,在同一评估切片中,在5例患者的亚组中,B7-H1阳性肿瘤区域的TILs明显少于B7-H1阴性肿瘤区域(P = 0.01)。此外,B7-H1阳性肿瘤区域中表达PD-1的TILs百分比明显低于B7-H1阴性肿瘤区域(P = 0.02)。

结论

局部肿瘤细胞上B7-H1的表达与TILs数量呈负相关,这可能有助于非小细胞肺癌抗肿瘤免疫反应的负性调节。

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