Ceramide participates in lysosome-mediated cell death induced by type II anti-CD20 monoclonal antibodies.
Considering the variable and often modest therapeutic efficacy of rituximab for a substantial proportion of patients suffering from non-Hodgkin lymphomas (NHLs), various type II anti-CD20 monoclonal antibodies (mAbs) with excellent ability in inducing programmed cell death (PCD) are currently being developed for their enhanced therapeutic index. Although homotypic adhesion (HA) and lysosome leakage are proven to be of vital importance in type II mAb-induced PCD in NHL cells, the detailed relationship between them remains unclear. Herein, for the first time we discovered that improved intracellular ceramide level is an important mediator between HA and lysosome leakage in tositumomab-induced cell death. Further experimental results revealed that the generation of intracellular ceramide acts as the outcome of HA and major cause of lysosome leakage. The clarification of ceramide involvement in type II anti-CD20 mAb-induced PCD may provide new ideas on CD20-based immunotherapy against NHLs.
Department of Otolaryngology, Tianjin Medical University General Hospital , Tianjin , China.
Yuzhi
Y
Liu
Ling
L
Shu
Jingjing
J
Wu
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002401:Cathepsin B / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism*; D000069283:Rituximab / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D002518:Ceramides; D000069283:Rituximab; D002401:Cathepsin B; C119496:tositumomab I-131
CD20; Non-Hodgkin lymphoma; ceramide; homotypic adhesion; lysosome leakage; programmed cell death