Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer

Abstract Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player in immunotherapy-related resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy. Metabolic adaption of CSCs drives tumor resistance, yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive. Here, through metabolomics, transcriptomics, a lung epithelial-specific Cpt1a -knockout mouse model, and clinical analysis, we…

• NN
  National Natural Science Foundation of China

  Awards: 82373100, 82273220, 81972795
• MO
  Ministry of Science and Technology of the People's Republic of China

  Award: 2018YFE0114300
• FR
  Fundamental Research Funds for the Central Universities