Dendritic Cells and Malignant Plasma Cells: An Alliance in Multiple Myeloma Tumor Progression?

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Describe defective immunological features that have been identified in dendritic cells in multiple myeloma and explain how immunologic dendritic cell defects could reduce the clinical efficacy of dendritic cell-based vaccines.Outline possible therapeutic strategies based on current knowledge of the bone marrow crosstalk between myeloma cells and immature dendritic cells. CME This article is available for continuing medical education credit at CME.TheOncologist.com 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.