The link between bone microenvironment and immune cells in multiple myeloma: Emerging role of CD38.

The relationship between bone and immune cells is well established both in physiological and pathological conditions. Multiple myeloma (MM) is a plasma cell malignancy characterized by an increase of number and activity of osteoclasts (OCLs) and a decrease of osteoblasts (OBs). These events are responsible for bone lesions of MM patients. OCLs support MM cells survival in vitro and in vivo. Recently, the possible role of OCLs as immunosuppressive cells in the MM BM microenvironment has been underlined. OCLs protect MM cells against T cell-mediated cytotoxicity through the expression of several molecules including programmed death-ligand (PD-L) 1, galectin (Gal) 9, CD200, and indoleamine-2,3-dioxygenase (IDO). Among the molecules that could be involved in the link between immune-microenvironment and osteoclastogenesis the role of CD38 has been hypothesized. CD38 is a well-known adhesion molecule and an ectoenzyme highly expressed by MM cells. Moreover, CD38 is expressed by OCLs and at the surface level on OCL precursors. Targeting CD38 with monoclonal antibodies showed inhibition of both osteoclastogenesis and OCL-mediated suppression of T cell function. This review elucidates this evidence indicating that osteoclastogenesis affect MM immune-microenvironment being a potential target to improve anti-MM immunity and to ameliorate bone disease.