title: CD137 signaling in Hodgkin and Reed-Sternberg cell lines induces IL-13 secretion, immune deviation and enhanced growth.
abstract: CD137 and its ligand, CD137L, are expressed on activated T cells and antigen-presenting cells (APC), respectively, and are powerful inducers of cellular, type 1 immune responses. CD137 is ectopically expressed by Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells in Hodgkin lymphoma (HL). Here we report that CD137 transmits signals into HRS cells, which induce the secretion of IL-13. IL-13 in conditioned supernatants of HRS cell lines inhibits the secretion of IFNγ by peripheral blood mononuclear cells (PBMC). Since IFNγ is essential for the development of a type 1 immune response, CD137-induced IL-13 secretion facilitates escape from immune surveillance. Further, CD137-induced IL-13 enhances the growth of HRS cell lines. CD137, IL-13 double-positive cells could be detected in the majority (58%) of HL patient samples, providing clinical evidence for a role of IL-13 induction by CD137 during HL pathogenesis. This study validates CD137 as a candidate target for immunotherapy of HL.
authors.affiliation: Department of Physiology.
authors.forename: Sakthi
authors.initials: S
authors.lastname: Rajendran
authors.affiliation: Department of Physiology.
authors.forename: Weng Tong
authors.initials: WT
authors.lastname: Ho
authors.affiliation: Department of Physiology; NUS Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
keywords: CD137; Hodgkin Lymphoma; IL-13; immune deviation; immune escape; proliferation