EPSTEIN-BARR VIRUS-INDUCED CD137 IN NASOPHARYNGEAL CARCINOMA

Abstract

Epstein-Barr virus (EBV) is associated with malignancies such as nasopharyngeal carcinoma (NPC) and classical Hodgkin lymphoma (cHL). Both undifferentiated NPC and cHL display EBV infection and a rich lymphoid stroma, thus it was hypothesized that NPC may also present EBV-induced ectopic CD137 expression for immune evasion as observed in cHL. NPC tissue array staining showed 39/116 cases with epithelial cells co-expressing an EBV marker and CD137. CD137 expression was induced in NPC cell lines transfected with EBV oncoprotein LMP1. Stable CD137 expressing NPC cell lines (CD137+ NPC) downregulated CD137L expressed on APCs when co-cultured together, emulating the CD137/CD137L negative feedback mechanism observed in immune cells. Expression of Frizzled 6, a receptor for soluble Wnt ligands and implicated in metastasis, doubled in proteome analysis of CD137 activated CD137+ NPC cells. CD137 targeting chimeric antigen receptor T cells displayed target cell killing, potential immunotherapy for the treatment of recurrent NPC.