國家衛生研究院 NHRI:Item 3990099045/15728
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 907902      Online Users : 914
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15728


    Title: Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer
    Authors: Ma, L;Chen, C;Zhao, CX;Li, T;Ma, LY;Jiang, JY;Duan, ZJ;Si, Q;Chuang, TH;Xiang, R;Luo, YP
    Contributors: Immunology Research Center
    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 demonstrate that CPT1A, a key rate-limiting enzyme of fatty acid oxidation, acts with L-carnitine, derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation in lung cancer. Mechanistically, CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating, thereby suppressing ferroptosis in CSCs. Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.
    Date: 2024-03-07
    Relation: Signal Transduction and Targeted Therapy. 2024 Mar 07;9:Article number 64.
    Link to: http://dx.doi.org/10.1038/s41392-024-01772-w
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2095-9907&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85187105610
    Appears in Collections:[Tsung-Hsien Chuang] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    ISI001180561900001.pdf7286KbAdobe PDF109View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback