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

doi:10.1016/j.ccr.2009.08.019

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: Journal article (peer-reviewed) › Journal article

251 Citations (Scopus)

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 language	English
Pages (from-to)	309-323
Number of pages	15
Journal	Cancer Cell
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2009.08.019
Publication status	Published - 06 Oct 2009
Externally published	Yes

Keywords

Animals
Antineoplastic Agents/pharmacology
Apoptosis
Bone Marrow Cells/drug effects
Boronic Acids/pharmacology
Bortezomib
Case-Control Studies
Cell Communication/drug effects
Cell Proliferation
Cell Survival
Chemotaxis
Coculture Techniques
Cytokines/metabolism
Dendritic Cells/drug effects
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Immunophenotyping
Mice
Mice, SCID
Multiple Myeloma/drug therapy
Oligodeoxyribonucleotides/pharmacology
Protease Inhibitors/pharmacology
Proteasome Endopeptidase Complex/metabolism
Pyrazines/pharmacology
Receptors, Immunologic/metabolism
Signal Transduction/drug effects
T-Lymphocytes/immunology
Time Factors
Toll-Like Receptors/drug effects
Transplantation, Heterologous
Tumor Cells, Cultured

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10.1016/j.ccr.2009.08.019

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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

@article{755d4af6bf0c4cbb8d5be8baf61e7140,

title = "Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target",

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.",

keywords = "Animals, Antineoplastic Agents/pharmacology, Apoptosis, Bone Marrow Cells/drug effects, Boronic Acids/pharmacology, Bortezomib, Case-Control Studies, Cell Communication/drug effects, Cell Proliferation, Cell Survival, Chemotaxis, Coculture Techniques, Cytokines/metabolism, Dendritic Cells/drug effects, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic, Humans, Immunophenotyping, Mice, Mice, SCID, Multiple Myeloma/drug therapy, Oligodeoxyribonucleotides/pharmacology, Protease Inhibitors/pharmacology, Proteasome Endopeptidase Complex/metabolism, Pyrazines/pharmacology, Receptors, Immunologic/metabolism, Signal Transduction/drug effects, T-Lymphocytes/immunology, Time Factors, Toll-Like Receptors/drug effects, Transplantation, Heterologous, Tumor Cells, Cultured",

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

year = "2009",

month = oct,

day = "6",

doi = "10.1016/j.ccr.2009.08.019",

language = "English",

volume = "16",

pages = "309--323",

journal = "Cancer Cell",

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Chauhan, D, Singh, AV, Brahmandam, M, Carrasco, R, Bandi, M, Hideshima, T, Bianchi, G, Podar, K, Tai, Y-T, Mitsiades, C, Raje, N, Jaye, DL, Kumar, SK, Richardson, P, Munshi, N & Anderson, KC 2009, 'Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target', Cancer Cell, vol. 16, no. 4, pp. 309-323. https://doi.org/10.1016/j.ccr.2009.08.019

TY - JOUR

T1 - Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells

T2 - a therapeutic target

AU - Chauhan, Dharminder

AU - Singh, Ajita V

AU - Brahmandam, Mohan

AU - Carrasco, Ruben

AU - Bandi, Madhavi

AU - Hideshima, Teru

AU - Bianchi, Giada

AU - Podar, Klaus

AU - Tai, Yu-Tzu

AU - Mitsiades, Constantine

AU - Raje, Noopur

AU - Jaye, David L

AU - Kumar, Shaji K

AU - Richardson, Paul

AU - Munshi, Nikhil

AU - Anderson, Kenneth C

PY - 2009/10/6

Y1 - 2009/10/6

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents/pharmacology

KW - Apoptosis

KW - Bone Marrow Cells/drug effects

KW - Boronic Acids/pharmacology

KW - Bortezomib

KW - Case-Control Studies

KW - Cell Communication/drug effects

KW - Cell Proliferation

KW - Cell Survival

KW - Chemotaxis

KW - Coculture Techniques

KW - Cytokines/metabolism

KW - Dendritic Cells/drug effects

KW - Drug Resistance, Neoplasm

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Immunophenotyping

KW - Mice

KW - Mice, SCID

KW - Multiple Myeloma/drug therapy

KW - Oligodeoxyribonucleotides/pharmacology

KW - Protease Inhibitors/pharmacology

KW - Proteasome Endopeptidase Complex/metabolism

KW - Pyrazines/pharmacology

KW - Receptors, Immunologic/metabolism

KW - Signal Transduction/drug effects

KW - T-Lymphocytes/immunology

KW - Time Factors

KW - Toll-Like Receptors/drug effects

KW - Transplantation, Heterologous

KW - Tumor Cells, Cultured

UR - http://www.scopus.com/inward/record.url?scp=70349577375&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.08.019

DO - 10.1016/j.ccr.2009.08.019

M3 - Journal article

C2 - 19800576

SN - 1535-6108

VL - 16

SP - 309

EP - 323

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

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

Abstract

Keywords

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