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.
N1 - Funding Information:
This investigation was supported by NIH grants SPORE-P50100707, PO1-CA078378, and RO1CA050947, and by Myeloma Research Foundation. D.C. designed research, analyzed data, and wrote the manuscript; A.S. designed, interpreted, and performed most experiments; M.B. performed growth/survival assays; G.B. isolated normal plasma cells; R.C. and D.J. helped with IHC; T.H., S.H., P.R., Y.T., N.R., C.M., and N.M. provided clinical samples; and K.A. analyzed data and wrote the manuscript. We also thank Robert Schlossman, Bryan Ciccarelli, and Sagar Lonial for providing blood samples. We are thankful to Lay-Hong Ang for confocal microscopy, John F. Daley for FACS, and Sangeetha Battar, Gaurav Chetri, and David Vasir for technical help and insightful discussions.
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 - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=70349577375&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349577375&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2009.08.019
DO - 10.1016/j.ccr.2009.08.019
M3 - Article
C2 - 19800576
AN - SCOPUS:70349577375
SN - 1535-6108
VL - 16
SP - 309
EP - 323
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -