Targeting NF-κB prevents Schwann cell reprogramming and plexiform neurofibroma initiation in mouse model of Nf1

Transient NF-κB pathway blockade significantly delays plexiform neurofibroma formation in a mouse model where Nf1 loss drives Schwann cell reprogramming.

• Why it matters: Plexiform neurofibromas occur in about half of NF1 individuals, and tumorigenesis may require cellular rewiring rather than additional genetic lesions in mutant Schwann cells.
• What they did: Using multiplex imaging and flow cytometry, tumor Schwann cells were defined as CD44+;CD49f+ with increased EMP-associated gene transcription, induced by stressors or IKK2-mediated NF-κB activation.
• The result: In established tumors, MEK inhibition plus NF-κB blockade reduced tumor proliferation, tumor Schwann cells, immune populations, tumor cytokines, and tumor number, and single-agent NF-κB blockade delayed tumor formation.

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