Immunobiology and ImmunotherapyEverolimus restrains the IL-17A-dependent osteoclast-like transdifferentiation of dendritic cells in multiple myeloma

•Everolimus (EVR) restrains malignant osteoclastogenesis in multiple myeloma.•The IL-17A/IL-17RA cascade is partly blocked by EVR in osteoclast-like dendritic cells.•EVR should be considered for the treatment of cancer-related bone diseases.

Interleukin-17A (IL-17A) promotes the osteoclast (OC)-like differentiation of dendritic cells (DCs) in multiple myeloma (MM) and contributes to the pathogenesis of myeloma bone disease (MBD). In our study, everolimus (EVR) abrogated the in vitro OC-like activity of DCs from 12 MM patients significantly. Exploring the EVR effects, we found that the inhibition of the osteoerosive activity of OC-DCs was mostly due to the blockade of signals driven by the IL-17A receptor toward the CCAAT/enhancer-binding protein beta/musculoaponeurotic fibrosarcoma oncogene homolog B axis Therefore, MM patients with MBD would probably benefit from mammalian target of rapamycin inhibition.