CD40 induces antigen transporter and immunoproteasome gene expression in carcinomas via the coordinated action of NF-kappaB and of NF-kappaB-mediated de novo synthesis of IRF-1.

Cancer cells may evade immune surveillance as a result of defective antigen processing and presentation. In this study, we demonstrate that CD40 ligation overcomes this defect through the coordinated action of the transcription factors NF-kappaB and interferon regulatory factor 1 (IRF-1). We show that unlike interferon signaling, which triggers the STAT1-mediated transcriptional activation of IRF-1, the ligation of CD40 in carcinomas induces the rapid upregulation of IRF-1 in a STAT1-independent but NF-kappaB-dependent manner.