Sun Liangjie, Zhao Guo, Wang Shuhang, Li Ning
Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Chin J Cancer Res. 2025 Jun 30;37(3):432-445. doi: 10.21147/j.issn.1000-9604.2025.03.11.
Drug resistance continues to be the principal limiting factor in achieving a cure for patients with cancer, significantly hindering the long-term efficacy of novel cancer drugs. Accumulating evidence has shown that metabolites derived from tumor cells regulate immune cell metabolism via tumor microenvironment crosstalk. However, as immunometabolic research has deepened, the leading role played by the intrinsic metabolic regulation of immune cells in the drug resistance of tumor cells has been discovered. Immune metabolites have been shown to cause immune resistance, target therapy resistance, and chemotherapy resistance, and drugs that target immune metabolism have great potential. To date, researchers have not fully explored the impact of immune-derived metabolites on tumor cells and their influence on the responsiveness to cancer drugs. In this review, we focus on the lactate, fatty acid, glucose, and nucleotide metabolic alterations that take place in T cells and macrophages and how these changes can impair anti-tumor immunity, ultimately promoting tumor cell survival and decreasing responsiveness to the corresponding therapeutic approaches. We present the current developments in drugs targeting immunometabolic pathways and propose constructive suggestions, such as precise delivery to immune cell targets to enhance efficacy and safety, offering novel perspectives for cancer drug development.
耐药性仍然是实现癌症患者治愈的主要限制因素，严重阻碍了新型抗癌药物的长期疗效。越来越多的证据表明，肿瘤细胞衍生的代谢产物通过肿瘤微环境的相互作用调节免疫细胞代谢。然而，随着免疫代谢研究的深入，人们发现免疫细胞的内在代谢调节在肿瘤细胞耐药性中起主导作用。免疫代谢产物已被证明可导致免疫抵抗、靶向治疗抵抗和化疗抵抗，而针对免疫代谢的药物具有巨大潜力。迄今为止，研究人员尚未充分探索免疫衍生代谢产物对肿瘤细胞的影响及其对癌症药物反应性的影响。在这篇综述中，我们重点关注T细胞和巨噬细胞中发生的乳酸、脂肪酸、葡萄糖和核苷酸代谢改变，以及这些变化如何损害抗肿瘤免疫，最终促进肿瘤细胞存活并降低对相应治疗方法的反应性。我们介绍了靶向免疫代谢途径药物的当前进展，并提出了建设性建议，如精确递送至免疫细胞靶点以提高疗效和安全性，为癌症药物开发提供了新的视角。
