Epstein-Barr virus-encoded LMP1 induces ectopic CD137 expression on Hodgkin and Reed-Sternberg cells via the PI3K-AKT-mTOR pathway

被引:24
作者
Aravinth, Sneha Priya [1 ,2 ]
Rajendran, Sakthi [1 ,2 ]
Li, Yating [1 ,2 ]
Wu, Meihui [1 ,2 ]
Wong, Anna Hiu Yi [1 ,2 ]
Schwarz, Herbert [1 ,2 ]
机构
[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore
[2] Natl Univ Singapore, Inst Life Sci, NUS Immunol Programme, Singapore, Singapore
基金
英国医学研究理事会;
关键词
Hodgkin lymphoma; EBV; LMP1; CD137; CLASSICAL HODGKIN; 4-1BB; INTERLEUKIN-13; LYMPHOMA; DISEASE; GROWTH; TARGET; LIGAND; PI3K;
D O I
10.1080/10428194.2019.1607330
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
CD137 is a potent co-stimulatory molecule on activated T cells, and its ligand (CD137L) is expressed on antigen presenting cells (APC). Ectopic expression of CD137 has been identified on Hodgkin Reed-Sternberg (HRS) cells, the malignant cells in Hodgkin Lymphoma (HL), and CD137 on HRS cells was found to support growth of HRS cells and escape from immune surveillance. HRS cells are mostly derived from B cells, which poses the question of how B cells acquire ectopic CD137 expression during the transformation process. HL is associated with Epstein-Barr virus (EBV) infection. We show that the EBV latent membrane protein 1 (LMP1) induces expression of CD137 in HRS cell lines. In a HL tissue microarray, 96% of the CD137-positive HL cases stained positive for LMP1. LMP1 utilizes the PI3K-AKT-mTOR pathway for inducing CD137 expression. These findings support the role of EBV in HL pathogenesis.
引用
收藏
页码:2697 / 2704
页数:8
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