title: Dendritic cells and malignant plasma cells: an alliance in multiple myeloma tumor progression?
abstract: The crosstalk of myeloma cells with accessory cells drives the expansion of malignant plasma cell clones and the hyperactivation of osteoclastogenesis that occurs in multiple myeloma (MM). These reciprocal interactions promote defective dendritic cell (DC) function in terms of antigen processing, clearance of tumor cells, and efficacy of the immune response. Thus, myeloma cells exert immune suppression that explains, at least in part, the failure of therapeutic approaches, including DC vaccination. Impairment of DCs depends on high bone marrow levels of cytokines and adhesion molecules that affect both maturation and expression of costimulatory molecules by DCs. Moreover, DCs share with osteoclasts (OCs) a common ontogenetic derivation from the monocyte lineage, and thus may undergo OC-like transdifferentiation both in vitro and in vivo. Immature DCs (iDCs) induce clonogenic growth of malignant plasma cells while displaying OC-like features, including the ability to resorb bone tissue once cultured with myeloma cells. This OC-like transdifferentiation of iDCs is dependent on the activation of both the receptor activator of nuclear factor κB (RANK)-RANK ligand (RANK-L) and CD47-thrombospondin (TSP)-I axes, although interleukin 17-producing T helper-17 clones within the bone microenvironment may also take part in this function. Therefore, iDCs allied with malignant plasma cells contribute to MM osteoclastogenesis, although other molecules released by tumor cells may independently contribute to the bone-resorbing machinery.
authors.affiliation: IMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Aldo Moro, Italy. m.tucci@dimo.uniba.it
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Stucci
authors.forename: Sabino
authors.initials: S
authors.lastname: Strippoli
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology*