Department of Internal Medicine-Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Surgical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Immunol Rev. 2024 Jan;321(1):211-227. doi: 10.1111/imr.13276. Epub 2023 Sep 16.
Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), which correlates to the mitochondrial tricarboxylic acid (TCA) cycle, resulting in proteotoxic stress and eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts an indispensable role in cancer progression, which is considered a promising strategy for cancer therapy. Cancer immunotherapy has gained extensive attention owing to breakthroughs in immune checkpoint blockade; furthermore, cuproptosis is strongly connected to the modulation of antitumor immunity. Thus, a thorough recognition concerning the mechanisms involved in the modulation of copper metabolism and cuproptosis may facilitate improvement in cancer management. This review outlines the cellular and molecular mechanisms and characteristics of cuproptosis and the links of the novel regulated cell death modality with human cancers. We also review the current knowledge on the complex effects of cuproptosis on antitumor immunity and immune response. Furthermore, potential agents that elicit cuproptosis pathways are summarized. Lastly, we discuss the influence of cuproptosis induction on the tumor microenvironment as well as the challenges of adding cuproptosis regulators to therapeutic strategies beyond traditional therapy.
铜是维持酶活性和转录因子功能的必需营养素。过量的铜会导致脂酰化二氢乳清酸 S-乙酰转移酶(DLAT)聚集,这与线粒体三羧酸(TCA)循环有关,导致蛋白毒性应激,并引发一种新的细胞死亡方式:铜死亡。铜死亡在癌症进展中发挥着不可或缺的作用,被认为是癌症治疗的一种有前途的策略。癌症免疫疗法因免疫检查点阻断的突破而受到广泛关注;此外,铜死亡与抗肿瘤免疫的调节密切相关。因此,深入了解调节铜代谢和铜死亡的机制可能有助于改善癌症的管理。本综述概述了铜死亡的细胞和分子机制和特征,以及这种新的调控细胞死亡方式与人类癌症的联系。我们还回顾了铜死亡对抗肿瘤免疫和免疫反应的复杂影响的现有知识。此外,总结了诱导铜死亡途径的潜在药物。最后,我们讨论了诱导铜死亡对肿瘤微环境的影响,以及在传统治疗之外的治疗策略中添加铜死亡调节剂所面临的挑战。
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