免疫检查点抑制剂（ICB）不仅针对CTLA-4、PD-1和PD-L1，还有新型的LAG-3药物已经在临床应用中获得批准。随着该药物的广泛使用，我们必须深入分析这些药物的困境，并在治疗前景中寻求突破。在过去的几十年中，这些药物在黑色素瘤和非小细胞肺癌（NSCLC）患者中展示了显著的疗效。然而，在广义固体肿瘤的范畴中，非特异性适应症、不可分割的免疫反应和副作用、未确认的进展性疾病以及复杂的免疫耐药调节网络是限制其广泛应用的四个障碍。幸运的是，新型ICB药物和联合疗法的成功临床试验，肿瘤溶瘤病毒基因编辑时代的到来以及mRNA疫苗和纳米传递系统技术障碍的突破，目前取得了显著突破。在本综述中，我们列举了每个免疫检查点靶点的机制，ICB与肿瘤突变负荷、关键免疫调节或耐药信号通路的关联，古典靶点和新靶点在不同肿瘤类型中的特定临床证据，并提出对药物安全的辩证思考。最后，我们讨论了基于最新预测生物标志物和诊断测试技术的准确分流ICB的重要性。©2023. 四川大学华西医院.

Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel targeting LAG-3 drugs have also been approved in clinical application. With the widespread use of the drug, we must deeply analyze the dilemma of the agents and seek a breakthrough in the treatment prospect. Over the past decades, these agents have demonstrated dramatic efficacy, especially in patients with melanoma and non-small cell lung cancer (NSCLC). Nonetheless, in the field of a broad concept of solid tumours, non-specific indications, inseparable immune response and side effects, unconfirmed progressive disease, and complex regulatory networks of immune resistance are four barriers that limit its widespread application. Fortunately, the successful clinical trials of novel ICB agents and combination therapies, the advent of the era of oncolytic virus gene editing, and the breakthrough of the technical barriers of mRNA vaccines and nano-delivery systems have made remarkable breakthroughs currently. In this review, we enumerate the mechanisms of each immune checkpoint targets, associations between ICB with tumour mutation burden, key immune regulatory or resistance signalling pathways, the specific clinical evidence of the efficacy of classical targets and new targets among different tumour types and put forward dialectical thoughts on drug safety. Finally, we discuss the importance of accurate triage of ICB based on recent advances in predictive biomarkers and diagnostic testing techniques.© 2023. West China Hospital, Sichuan University.