Functional Interaction of Plasmacytoid Dendritic Cells with Multiple Myeloma Cells: A Therapeutic Target

Dharminder Chauhan, Ajita V. Singh, Mohan Brahmandam, Ruben Carrasco, Madhavi Bandi, Teru Hideshima, Giada Bianchi, Klaus Podar, Yu Tzu Tai, Constantine Mitsiades, Noopur Raje, David L. Jaye, Shaji K. Kumar, Paul Richardson, Nikhil Munshi, Kenneth C. Anderson

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Multiple myeloma (MM) remains incurable despite novel therapies, suggesting the need for further identification of factors mediating tumorigenesis and drug resistance. Using both in vitro and in vivo MM xenograft models, we show that plasmacytoid dendritic cells (pDCs) in the bone marrow (BM) microenvironment both mediate immune deficiency characteristic of MM and promote MM cell growth, survival, and drug resistance. Microarray, cell signaling, cytokine profile, and immunohistochemical analysis delineate the mechanisms mediating these sequelae. Although pDCs are resistant to novel therapies, targeting Toll-like receptors with CpG oligodeoxynucleotides both restores pDC immune function and abrogates pDC-induced MM cell growth. Our study therefore validates targeting pDC-MM interactions as a therapeutic strategy to overcome drug resistance in MM.

Original languageEnglish (US)
Pages (from-to)309-323
Number of pages15
JournalCancer cell
Volume16
Issue number4
DOIs
StatePublished - Oct 6 2009

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Chauhan, D., Singh, A. V., Brahmandam, M., Carrasco, R., Bandi, M., Hideshima, T., Bianchi, G., Podar, K., Tai, Y. T., Mitsiades, C., Raje, N., Jaye, D. L., Kumar, S. K., Richardson, P., Munshi, N., & Anderson, K. C. (2009). Functional Interaction of Plasmacytoid Dendritic Cells with Multiple Myeloma Cells: A Therapeutic Target. Cancer cell, 16(4), 309-323. https://doi.org/10.1016/j.ccr.2009.08.019