Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target.

Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target.
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DOI:
10.1016/j.ccr.2009.08.019
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发表时间:
2009-10-06
期刊:
影响因子:
50.3
通讯作者:
Anderson KC
Anderson KC
中科院分区:
医学1区
文献类型:
--
作者:
Chauhan D;Singh AV;Brahmandam M;Carrasco R;Bandi M;Hideshima T;Bianchi G;Podar K;Tai YT;Mitsiades C;Raje N;Jaye DL;Kumar SK;Richardson P;Munshi N;Anderson KC

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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 ODNs 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.
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