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Interleukin-30 promotes melanoma spreading and triggers LAG-3 expression and T cell exhaustion - PubMed

4 days ago
  • #Melanoma
  • #T cell exhaustion
  • #Interleukin-30
  • Interleukin-30 (IL30) promotes melanoma spreading and metastasis.
  • IL30 is absent in normal skin but present in melanoma and immune cells, particularly macrophages.
  • IL30 receptor complex (IL-6Rα/gp130) is expressed by melanoma cells, enhancing proliferation and migration.
  • IL30 upregulates metastasis-associated genes (ANG2, CXCR4, ITGB1, MMP2, NME, SNAI2, VEGFA, VEGFC, L1CAM).
  • Higher IL30 expression is found in metastases compared to primary tumors.
  • IL30 induces immune checkpoint molecules (LSECtin, LGALS3, LGALS9, LAG-3, TIM-3, B7-H4, B7-H3, VISTA, PD-1).
  • IL30 suppresses T cell function by reducing CD25 and HLA-DR expression, inhibiting activation and proliferation.
  • IL30 decreases TNF-α and IFN-γ production in T cells and boosts LAG-3 expression.
  • IL30 levels strongly correlate with LAG-3 expression in clinical samples.
  • IL30 is identified as a critical driver of melanoma dissemination and T cell exhaustion.