Enhancement of clonogenicity of human multiple myeloma by dendritic cells.
Infiltration by dendritic cells (DCs) is a common feature of most human tumors. Prior studies evaluating the interaction of DCs with tumors have focused largely on their immunologic properties (for review see Banchereau, J., and R.M. Steinman. 1998. Nature. 392:245-252). In this study, we show that the clonogenicity of several human tumor cell lines and primary tumor cells from myeloma patients is enhanced by their interactions with DCs. Myeloma cells cultured in the presence of DCs have an altered phenotype with an increased proportion of cells lacking terminal plasma cell differentiation marker CD138. DC-tumor interaction also leads to the up-regulation of B cell lymphoma 6 expression in myeloma cells. Effects of DCs on myeloma cells are inhibited by blockade of the receptor activator of NF-kB (RANK)-RANK ligand and B cell-activating factor-APRIL (a proliferation-inducing ligand)-mediated interactions. Together, these data suggest that tumor-DC interactions may directly impact the biology of human tumors, particularly multiple myeloma, and may be a target for therapeutic intervention.
Kukreja
Anjli
A
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
Hutchinson
Aisha
A
Dhodapkar
Kavita
K
Mazumder
Amitabha
A
Vesole
David
D
Angitapalli
Revathi
R
Jagannath
Sundar
S
Dhodapkar
Madhav V
MV
D001853:Bone Marrow / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans