Enhancement of clonogenicity of human multiple myeloma by dendritic cells

• Authors: Anjil Kukreja, Rockefeller University; Aisha Hutchinson, Rockefeller University; Kavita Dhodapkar, Emory University; Amitabha Mazumder, St. Vincent's Cancer Center; David Vesole, St. Vincent's Cancer Center; Revathi Angitapalli, Rockefeller University; Sundar Jagannath, St. Vincent's Cancer Center; Madhav Dhodapkar, Emory University
• Journal Title: Journal of Experimental Medicine
• Volume: Volume 203, Number 8
• Publisher: Rockefeller University Press | 2006-08-07, Pages 1859-1865
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1084/jem.20052136
• Subjects: Health Sciences, Immunology; Biology, Genetics; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; PROMOTE TUMOR PROGRESSION; BONE-MARROW; GENE-EXPRESSION; GROWTH; DIFFERENTIATION; CANCER; BAFF; MICROENVIRONMENT; LOCALIZATION; MATURATION

Abstract

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.