Author/Authors :
Wilson، نويسنده , , Nicholas S. and Yang، نويسنده , , Becky and Yang، نويسنده , , Annie and Loeser، نويسنده , , Stefanie and Marsters، نويسنده , , Scot and Lawrence، نويسنده , , David and Li، نويسنده , , Yun and Pitti، نويسنده , , Robert and Totpal، نويسنده , , Klara and Yee، نويسنده , , Sharon Cutler Ross، نويسنده , , Sarajane and Vernes، نويسنده , , Jean-Michel and Lu، نويسنده , , Yanmei and Adams، نويسنده , , Cam and Offringa، نويسنده , , Rienk and Kelley، نويسنده , , Bob and Hymowitz، نويسنده , , Sarah I.F. Daniel، نويسنده , , Dylan and Meng، نويسنده , , Gloria and Ashkenazi، نويسنده , , Avi، نويسنده ,
Abstract :
Summary
dies to cell-surface antigens trigger activatory Fcγ receptor (FcγR)-mediated retrograde signals in leukocytes to control immune effector functions. Here, we uncover an FcγR mechanism that drives antibody-dependent forward signaling in target cells. Agonistic antibodies to death receptor 5 (DR5) induce cancer-cell apoptosis and are in clinical trials; however, their mechanism of action in vivo is not fully defined. Interaction of the DR5-agonistic antibody drozitumab with leukocyte FcγRs promoted DR5-mediated tumor-cell apoptosis. Whereas the anti-CD20 antibody rituximab required activatory FcγRs for tumoricidal function, drozitumab was effective in the context of either activatory or inhibitory FcγRs. A CD40-agonistic antibody required similar FcγR interactions to stimulate nuclear factor-κB activity in B cells. Thus, FcγRs can drive antibody-mediated receptor signaling in target cells.
