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Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target.
- Source :
-
Cancer cell [Cancer Cell] 2009 Oct 06; Vol. 16 (4), pp. 309-23. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Apoptosis
Bone Marrow Cells drug effects
Bone Marrow Cells pathology
Boronic Acids pharmacology
Bortezomib
Case-Control Studies
Cell Proliferation
Cell Survival
Chemotaxis
Coculture Techniques
Cytokines metabolism
Dendritic Cells drug effects
Dendritic Cells pathology
Gene Expression Regulation, Neoplastic
Humans
Immunophenotyping
Mice
Mice, SCID
Multiple Myeloma drug therapy
Multiple Myeloma genetics
Multiple Myeloma pathology
Oligodeoxyribonucleotides pharmacology
Protease Inhibitors pharmacology
Proteasome Endopeptidase Complex metabolism
Pyrazines pharmacology
Receptors, Immunologic metabolism
T-Lymphocytes immunology
Time Factors
Toll-Like Receptors drug effects
Toll-Like Receptors metabolism
Transplantation, Heterologous
Tumor Cells, Cultured
Bone Marrow Cells immunology
Cell Communication drug effects
Dendritic Cells immunology
Drug Resistance, Neoplasm
Multiple Myeloma immunology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 16
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 19800576
- Full Text :
- https://doi.org/10.1016/j.ccr.2009.08.019