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

被引：227

作者：

Chauhan, Dharminder ^{[1
,2
]}

Singh, Ajita V. ^{[1
,2
]}

Brahmandam, Mohan ^{[1
,2
]}

Carrasco, Ruben ^{[1
,2
]}

Bandi, Madhavi ^{[1
,2
]}

Hideshima, Teru ^{[1
,2
]}

Bianchi, Giada ^{[1
,2
]}

Podar, Klaus ^{[1
,2
]}

Tai, Yu-Tzu ^{[1
,2
]}

Mitsiades, Constantine ^{[1
,2
]}

Raje, Noopur ^{[1
,2
]}

Jaye, David L. ^{[3
]}

Kumar, Shaji K. ^{[4
]}

Richardson, Paul ^{[1
,2
]}

Munshi, Nikhil ^{[5
]}

Anderson, Kenneth C. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Myeloma Res,Dept Med Oncol, Boston, MA 02115 USA

[3] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[4] Mayo Clin, Dept Hematol, Rochester, MN 55905 USA

[5] Harvard Univ, Sch Med, Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA

来源：

CANCER CELL | 2009年 / 16卷 / 04期

关键词：

INTERFERON-PRODUCING CELLS; REGULATORY T-CELLS; BONE-MARROW; NUCLEIC-ACIDS; HUMAN BLOOD; EXPRESSION; SURVIVAL; INDUCE; DIFFERENTIATION; INTERLEUKIN-6;

D O I：

10.1016/j.ccr.2009.08.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：309 / 323

页数：15

共 49 条

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