免疫检查点抑制剂（ICI）在癌症治疗中取得了前所未有的临床成功。然而，对ICI治疗的药物耐药性是阻碍癌症患者对治疗作出反应或持久控制疾病的主要障碍。药物再利用是指将已临床批准的药物，具有特定药理特性和已知不良反应谱，用于新的适应症。它也成为克服药物耐药性的一种有希望的策略。在本综述中，我们总结了关于利用药物再利用来克服ICI耐药性的最新研究。再利用的药物通过具有免疫刺激活性或消除免疫抑制性肿瘤微环境（TME）的方式发挥作用。与从头设计药物策略相比，它们提供了新颖且经济实惠的癌症免疫治疗选项，可在临床中方便进行评估。利用生物标志物来识别适应于再利用药物和药物组合的正确患者人群。已经进行了化学库的表型筛选，以寻找T细胞修饰药物。采用基因组学和整合生物信息学分析、人工智能、机器和深度学习方法等来识别免疫抑制TME的新调节因子。

Immune checkpoint inhibitors (ICI) have achieved unprecedented clinical success in cancer treatment. However, drug resistance to ICI therapy is a major hurdle that prevents cancer patients from responding to the treatment or having durable disease control. Drug repurposing refers to the application of clinically approved drugs, with characterized pharmacological properties and known adverse effect profiles, to new indications. It has also emerged as a promising strategy to overcome drug resistance. In this review, we summarized the latest research about drug repurposing to overcome ICI resistance. Repurposed drugs work by either exerting immunostimulatory activities or abolishing the immunosuppressive tumor microenvironment (TME). Compared to the de novo drug design strategy, they provide novel and affordable treatment options to enhance cancer immunotherapy that can be readily evaluated in the clinic. Biomarkers are exploited to identify the right patient population to benefit from the repurposed drugs and drug combinations. Phenotypic screening of chemical libraries has been conducted to search for T-cell-modifying drugs. Genomics and integrated bioinformatics analysis, artificial intelligence, machine and deep learning approaches are employed to identify novel modulators of the immunosuppressive TME.