Research article summary (published 4 Oct 2009):

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

Full 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.

Author information

Author/s: Chauhan, Dharminder (D); Singh, Ajita V (AV); Brahmandam, Mohan (M); Carrasco, Ruben (R); Bandi, Madhavi (M); Hideshima, Teru (T); Bianchi, Giada (G); Podar, Klaus (K); Tai, Yu-Tzu (YT); Mitsiades, Constantine (C); Raje, Noopur (N); Jaye, David L (DL); Kumar, Shaji K (SK); Richardson, Paul (P); Munshi, Nikhil (N); Anderson, Kenneth C (KC);

Affiliation: The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma Research, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. dharminder_chauhan(-atsign-)dfci.harvard.edu

Grants: P01-CA078378 (Agency:NCI NIH HHS) ; P50100707 (Agency:PHS HHS) ; R01CA050947 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Cancer cell (Cancer Cell), published in United States. (Language: eng)

Reference: 2009-Oct; vol 16 (issue 4) : pp 309-23

Dates: Created 2009/10/05; Completed 2009/10/15; Revised 2009/10/16;

PMID: 19800576, status: MEDLINE (last retrieval date: 10/19/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents - pharmacology Apoptosis Bone Marrow Cells - drug effects; immunology; pathology Boronic Acids - pharmacology Case-Control Studies Cell Communication - drug effects Cell Proliferation Cell Survival Chemotaxis Coculture Techniques Cytokines - metabolism Dendritic Cells - drug effects; immunology; pathology Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic Humans

Humans Immunophenotyping Mice Mice, SCID Multiple Myeloma - drug therapy; genetics; immunology; pathology 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; metabolism Transplantation, Heterologous Tumor Cells, Cultured

Associated Chemicals: Antineoplastic Agents (0) ; Boronic Acids (0) ; CPG-oligonucleotide (0) ; Cytokines (0) ; Oligodeoxyribonucleotides (0) ; Protease Inhibitors (0) ; Pyrazines (0) ; Receptors, Immunologic (0) ; Toll-Like Receptors (0) ; bortezomib (0) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)

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