Dendritic cells and malignant plasma cells: An alliance in multiple myeloma tumor progression?

Marco Tucci, Stefania Stucci, Sabino Strippoli, Franco Dammacco, Franco Silvestris

Research output: Contribution to journalArticlepeer-review

Abstract

The crosstalk of myeloma cells with accessory cells drives the expansion of malignant plasma cell clones and the hyperactivation of osteoclastogenesis that oc-cursinmultiple 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 levelsofcytokines and adhesion molecules that affect both maturation and expression of costimu-latory 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.

Original languageEnglish
Pages (from-to)1040-1048
Number of pages9
JournalThe oncologist
Volume16
Issue number7
DOIs
Publication statusPublished - Jul 2011

Keywords

  • Bone disease
  • Dendritic cells
  • Immune system
  • Multiple myeloma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Dendritic cells and malignant plasma cells: An alliance in multiple myeloma tumor progression?'. Together they form a unique fingerprint.

Cite this