Targeting brain macrophages: NF-κB as a therapeutic gateway in melanoma brain metastasis

Cancer Cell. 2025 Mar 10;43(3):328-329. doi: 10.1016/j.ccell.2025.02.020.

Abstract

Melanoma brain metastasis (MBM) is associated with poor prognosis. In this issue of Cancer Cell, Rodriguez-Baena et al. identify nuclear factor κB (NF-κB) (Rela) as a driver of pro-tumoral microglia in MBM. While Rela deletion reprograms microglia, enhancing proinflammatory and anti-metastasis T cell responses, RELA activation in human macrophages correlates with immunotherapy resistance.

MeSH terms

  • Animals
  • Brain / pathology
  • Brain Neoplasms* / immunology
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / secondary
  • Humans
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Melanoma* / drug therapy
  • Melanoma* / immunology
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Mice
  • Microglia / metabolism
  • NF-kappa B* / metabolism
  • Transcription Factor RelA* / metabolism

Substances

  • NF-kappa B
  • Transcription Factor RelA