Bortezomib disrupts tumour-dendritic cell interactions in myeloma and lymphoma: therapeutic implications.
Recent studies have shown that the interactions between tumour and dendritic cells (DCs) promote clonogenic growth of lymphoproliferative tumours, particularly myeloma. The present study showed that the proteasome inhibitor, bortezomib, disrupts this interaction. Targeting the drug to DCs was required for optimal suppression of tumour growth, including primary myeloma tumour progenitors in clonogenic assays. Bortezomib lead to dose-dependent induction of apoptosis in both myeloid and plasmacytoid DCs, and the sensitivity of DCs to bortezomib was comparable with that of tumour cells. These data suggest that disruption of tumour-DC interactions may contribute to the clinical effects of bortezomib.
Kukreja
Anjli
A
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
Hutchinson
Aisha
A
Mazumder
Amitabha
A
Vesole
David
D
Angitapalli
Revathi
R
Jagannath
Sundar
S
O'connor
Owen A
OA
Dhodapkar
Madhav V
MV
D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay / Q000379:methods; D003713:Dendritic Cells / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib