Leukemia & lymphoma
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Leukemia & lymphoma · Jan 2011
A potential mechanism of rituximab-induced inhibition of tumor growth through its sensitization to tumor necrosis factor-related apoptosis-inducing ligand-expressing host cytotoxic cells.
Rituximab (anti-CD20 mAb) mediates antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis in B-NHL cells. The contribution of other host-mediated cytotoxic effects has not been examined. The expression of death-inducing ligands (e.g. ⋯ Rituximab-mediated sensitization to TRAIL apoptosis was due, in large part, to rituximab-mediated inhibition of the transcription factor Yin Yang 1 (YY1). The direct role of YY1 in TRAIL sensitization by rituximab was shown in cells transfected with YY1 siRNA, and such cells mimicked rituximab and became sensitive to TRAIL-induced apoptosis. These data suggest that, in vivo, host effector cells expressing TRAIL may contribute to rituximab-mediated depletion of B-NHL cells.