Activities of the cytokine receptor CD137 in multiple myeloma

Abstract

Multiple myeloma is an incurable hematological malignancy derived from B cells, and characterized by bone destruction and multiple organ dysfunctions. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) Receptor and TNF superfamilies, respectively. CD137 enhances proliferation and survival in healthy B cells. Since CD137 can be expressed as a neoantigen by certain B cell lymphomas, we hypothesized that CD137 may act as a growth factor for B cell lymphomas. Surprisingly, we found that CD137 has the opposite effects in multiple myeloma (MM) cells, where it inhibits proliferation and induces cell death by apoptosis. In contrast, CD137 does not significantly affect or enhance proliferation or survival in non-MM B cell lymphoma lines. Further secretion of IL-6 and IL-8 is also enhanced in MM but not in non-MM cell lines in response to CD137. A selective elimination of malignant B cells in MM patients by CD137 could help to slow down disease progression and reduce the doses (and hence side effects) in conjunction with conventional treatment regimes.