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

Abstract

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.

Keywords:

• Hodgkin lymphoma
• EBV
• LMP1
• CD137

Acknowledgments

We thank the LSI core facility under the leadership of Dr. Paul Hutchinson for excellent help with flow cytometry.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2019.1607330.

Additional information

Funding

This research was supported by a grant [OFIRG/0022/2016] from the National Medical Research Council Singapore.