EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy

被引：341

作者：

Fang, Wenfeng ^{[1
,2
]}

Zhang, Jianwei ^{[3
]}

Hong, Shaodong ^{[1
,2
]}

Zhan, Jianhua ^{[1
,2
]}

Chen, Nan ^{[4
]}

Qin, Tao ^{[1
,2
]}

Tang, Yanna ^{[4
]}

Zhang, Yaxiong ^{[1
,2
]}

Kang, Shiyang ^{[1
,2
]}

Zhou, Ting ^{[1
,2
]}

Wu, Xuan ^{[1
,2
]}

Liang, Wenhua ^{[1
,2
]}

Hu, Zhihuang ^{[1
,2
]}

Ma, Yuxiang ^{[1
,2
]}

Zhao, Yuanyuan ^{[1
,2
]}

Tian, Ying ^{[1
,2
]}

Yang, Yunpeng ^{[1
,2
]}

Xue, Cong ^{[1
,2
]}

Yan, Yue ^{[1
,2
]}

Hou, Xue ^{[1
,2
]}

Huang, Peiyu ^{[1
,2
]}

Huang, Yan ^{[1
,2
]}

Zhao, Hongyun ^{[1
,2
]}

Zhang, Li ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Oncol, Guangzhou 510275, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Affiliated Hosp 5, Dept Oncol, Zhuhai, Guangdong, Peoples R China

来源：

ONCOTARGET | 2014年 / 5卷 / 23期

基金：

国家高技术研究发展计划(863计划);

关键词：

Nasopharyngeal carcinoma (NPC); latent membrane protein 1 (LMP1); PD-L1; Epstein-Barr virus (EBV); EPSTEIN-BARR-VIRUS; LATENT MEMBRANE PROTEIN-1; HPV-ASSOCIATED HEAD; B7-H1; EXPRESSION; T-LYMPHOCYTES; CANCER; PATHWAY; CELLS; PATHOGENESIS; INFECTION;

D O I：

10.18632/oncotarget.2608

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-gamma pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-kappa B pathways. Besides, IFN-gamma was independent of but synergetic with LMP1 in up-regulating PD-L1 in NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients.

引用

页码：12189 / 12202

页数：14

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