铜是维持酶活性和转录因子功能的必需营养物质。过量的铜导致脂酰化二硫化硫辛酰转移酶（DLAT）的聚集，与线粒体三羧酸循环（TCA）相关，导致蛋白毒性应激并引发一种新型细胞死亡方式：铜死亡。铜死亡在癌症进展中起着不可或缺的作用，被认为是癌症治疗的一种有希望的策略。由于免疫检查点阻断的突破，癌症免疫疗法受到广泛关注。此外，铜死亡与抗肿瘤免疫的调节密切相关。因此，对铜代谢和铜死亡调节机制的全面认识可能促进癌症管理的改善。本综述概述了铜死亡的细胞和分子机制及其与人类癌症的关联特征。我们还回顾了铜死亡对抗肿瘤免疫和免疫应答的复杂效应。此外，总结了引发铜死亡通路的潜在药物。最后，我们讨论了铜死亡诱导对肿瘤微环境的影响，以及将铜死亡调节剂加入传统治疗以外的治疗策略的挑战。© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.