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Lactate-driven IL8+ Tumor-Associated Macrophages Mediate Immunosuppression and Resistance to Immunotherapy in Clear Cell Renal Cell Carcinoma - PubMed

2 months ago
  • #Tumor-Associated Macrophages
  • #Immunotherapy
  • #ccRCC
  • IL8+ Tumor-Associated Macrophages (TAMs) are linked to immunosuppression and resistance to immunotherapy in clear cell renal cell carcinoma (ccRCC).
  • High infiltration of IL8+ TAMs correlates with resistance to immune checkpoint blockade (ICB) in ccRCC.
  • IL8+ TAMs exhibit a glycolysis-associated metabolic program and are responsive to lactate, which promotes IL8 expression.
  • These TAMs display an immunosuppressive profile, leading to CD8+ T-cell dysfunction and regulatory T-cell accumulation.
  • Blocking IL8 ex vivo alleviates CD8+ T-cell exhaustion and enhances anti-PD-1 therapy efficacy.
  • Targeting IL8 may help overcome ICB resistance and improve immunotherapy outcomes in ccRCC.