IL-32 promotes proliferation and oxidative phosphorylation and is expressed in a subgroup of myeloma patients with poor prognosis and an immature plasma cell profile

IL-32 is a non-classical cytokine expressed in cancers, inflammatory diseases and infections. A receptor for IL-32 is not identified and how it acts at the molecular level is not understood. We here demonstrate that endogenously expressed, intracellular IL-32 interacts with components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in a myeloma cell line significantly reduced cancer cell survival and proliferation in vitro and in vivo. We propose a novel concept for regulation of metabolism by an intracellular cytokine and identify IL-32 as an endogenous growth and survival factor for malignant plasma cells.