Assuntos
Anticorpos Monoclonais Murinos/imunologia , Anticorpos Monoclonais/imunologia , Antígenos CD20/imunologia , Neutrófilos/imunologia , Espécies Reativas de Oxigênio/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Murinos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Células Cultivadas , Técnicas de Cocultura , Inibidores Enzimáticos/imunologia , Inibidores Enzimáticos/farmacologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Medições Luminescentes/métodos , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/imunologia , NADPH Oxidases/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Oniocompostos/imunologia , Oniocompostos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rituximab , Células Tumorais CultivadasRESUMO
The antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells is assumed to contribute to the clinical efficacy of monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL) and other hematopoietic malignancies of B cell origin. We sought to determine whether reactive oxygen species (ROS)-producing monocytes regulate the ADCC of NK cells against primary CLL cells using anti-CD20 as the linking antibody. The monoclonal CD20 antibodies rituximab and ofatumumab were found to trigger substantial release of ROS from monocytes. Antibody-exposed monocytes induced NK cell apoptosis and restricted NK cell-mediated ADCC against autologous CLL cells. The presence of inhibitors of ROS formation and scavengers of ROS preserved NK cell viability and restored NK cell-mediated ADCC against primary CLL cells. We propose that limiting the antibody-induced induction of immunosuppressive ROS may improve the anti-leukemic efficacy of anti-CD20 therapy in CLL.