TY - JOUR
T1 - Bortezomib disrupts tumour-dendritic cell interactions in myeloma and lymphoma
T2 - Therapeutic implications
AU - Kukreja, Anjli
AU - Hutchinson, Aisha
AU - Mazumder, Amitabha
AU - Vesole, David
AU - Angitapalli, Revathi
AU - Jagannath, Sundar
AU - O'Connor, Owen A.
AU - Dhodapkar, Madhav V.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Lymphoma
KW - Myeloid dendritic cells
KW - Myeloma
KW - Plasmacytoid dendritic cells
KW - Tumour microenvironment
UR - http://www.scopus.com/inward/record.url?scp=33845496508&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.2006.06369.x
DO - 10.1111/j.1365-2141.2006.06369.x
M3 - Article
C2 - 17222199
AN - SCOPUS:33845496508
SN - 0007-1048
VL - 136
SP - 106
EP - 110
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 1
ER -