Li Yunchang, Hu Lanlin, Peng Xinhao, Xu Huasheng, Tang Bo, Xu Chuan
Integrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan, China.
Authors contributed equally.
Cancer Drug Resist. 2022 Feb 8;5(1):129-146. doi: 10.20517/cdr.2021.102. eCollection 2022.
Non-small cell lung cancer (NSCLC) patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation are associated with significant clinical heterogeneity and a poor prognosis to standard NSCLC therapies such as surgical resection, radiotherapy, chemotherapies, and targeted medicines. However, the application of immune checkpoints inhibitors (ICIs) has dramatically altered the therapeutic pattern of NSCLC management. Clinical studies have indicated that some KRAS-mutant NSCLC patients could benefit from ICIs; however, the responses in some patients are still poor. This review intends to elucidate the mechanisms of resistance to immunotherapy in KRAS-driven NSCLC and highlight the TME functions altered by immunoinhibitors, immunostimulators, and cancer metabolism. These metabolic pathways could potentially be promising approaches to overcome immunotherapy resistance.
携带 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）突变的非小细胞肺癌（NSCLC）患者具有显著的临床异质性，并且对标准 NSCLC 治疗（如手术切除、放疗、化疗和靶向药物）的预后较差。然而，免疫检查点抑制剂（ICIs）的应用极大地改变了 NSCLC 的治疗模式。临床研究表明，一些 KRAS 突变的 NSCLC 患者可从 ICIs 中获益；然而，部分患者的反应仍然较差。本综述旨在阐明 KRAS 驱动的 NSCLC 中免疫治疗耐药的机制，并强调免疫抑制剂、免疫刺激剂和癌症代谢改变的肿瘤微环境（TME）功能。这些代谢途径可能是克服免疫治疗耐药的有前景的方法。
