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CD137 signaling in Hodgkin and Reed-Sternberg cell lines induces IL-13 secretion, immune deviation and enhanced

Sakthi Rajendran1, Weng Tong Ho1, Herbert Schwarz2

  • 1Department of Physiology.

Oncoimmunology
|July 30, 2016
PubMed

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.

Keywords:
CD137Hodgkin LymphomaIL-13immune deviationimmune escapeproliferation

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