Potential Tumor-promoting Effects of Ectopic CD137 Expression on Hodgkin Lymphoma

Abstract

Hodgkin and Reed Sternberg (HRS) cells in Hodgkin lymphoma (HL) were reported to express CD137 ectopically but its function(s) in pathogenesis of HL remained unidentified. This study shows that ectopic CD137 expression on HRS cells reduces IFN-? release from T cells by downregulating CD137L expression on HRS cells. The downregulation of CD137L is not due to a reduction of de novo synthesis of CD137L but due to an increased CD137L turnover. When CD137 binds to CD137L, the CD137-CD137L complex will be internalized, and hence reduces the surface CD137L levels available for T cell co-stimulation. Ectopic CD137 also get transferred from HRS cells to surrounding cells including B cells and monocytes and leads to the downregulation of CD137L on these APC. The CD137L downregulation on APC results in a lower T cell co-stimulation and a reduction of IFN-? release from T cells. In conclusion, this study provides new insights into the pathogenesis of HL.