ROLE OF CD137 SIGNALING IN IMMUNE DEVIATION OF HODGKIN LYMPHOMA AND ITS UTILISATION IN DEVELOPMENT OF IMMUNOTHERAPY

Abstract

CD137, a member of the tumor necrosis factor receptor (TNFR) superfamily has been reported to be ectopically expressed on Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells in Hodgkin lymphoma (HL). Here we report that, CD137 signaling in HRS cells induces the secretion of IL-13, a Th2 cytokine. IL-13 in conditioned supernatants from CD137-stimulated HRS cell lines inhibits the secretion of an essential Th1 cytokine, IFN-in peripheral blood mononuclear cells. Hence, CD137-induced IL-13 secretion facilitates escape of HRS cells from immune surveillance, through downregulation of IFN-Γ. Targeting CD137 can be a potential therapeutic option for HL patients. Bi-specific antibodies against CD137 and CD30 were generated and tested for their ability to preferentially lyse CD30+CD137+ HRS cells in vitro. To summarize, this study has identified CD137 signaling as a mechanism of immune deviation in HL, and evaluated the efficacy of bi-specific antibodies against CD30 and CD137 as a potential immunotherapy for HL.