CFLIP Inhibition Triggers Extrinsic Apoptosis in ABC Subtype Lymphoma Models

Diffuse large B-cell lymphoma represents the most common adult non-Hodgkin lymphoma, yet a significant portion of patients fail to achieve long-term remission with standard rituximab-based regimens [1]. Treatment resistance in these aggressive malignancies is frequently driven by the dysregulation of programmed cell death, a process that normally eliminates damaged or oncogenic cells [2]. While much clinical attention has focused on the intrinsic apoptotic pathway and the use of BCL-2 inhibitors to restore cellular suicide, many tumors utilize alternative mechanisms to evade immune-mediated destruction [3, 4]. Furthermore, the activation of pro-survival transcription factors such as NF-kappaB often creates an inflammatory microenvironment that further protects malignant B cells from therapy [5, 6]. Understanding the precise molecular barriers to extrinsic apoptosis is essential for developing the next generation of precision therapies for refractory disease.