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

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• 作者：Dharminder Chauhan ; Ajita V. Singh ; Mohan Brahm ; am ; Ruben Carrasco ; Madhavi B ; i ; 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
• 刊名：Cancer Cell
• 出版年：2009
• 出版时间：6 October 2009
• 年：2009
• 卷：16
• 期：4
• 页码：309-323
• 全文大小：2358 K

文摘

Summary

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.