Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends.
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends.
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DOI：
10.1038/s41392-023-01522-4
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发表时间：
2023-08-28
影响因子：
39.3
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Sun, Qian;Hong, Zhenya;Zhang, Cong;Wang, Liangliang;Han, Zhiqiang;Ma, Ding
免疫检查点抑制剂（ICB），除了靶向CTLA-4、PD-1和PD-L1外，新型靶向LAG-3药物也已获批临床应用。随着药物的广泛使用，我们必须深入分析药物的困境，寻求治疗前景的突破。在过去的几十年里，这些药物已经证明了显着的疗效，特别是在黑色素瘤和非小细胞肺癌（NSCLC）患者。尽管如此，在实体瘤的广泛概念领域，非特异性适应症，不可分割的免疫反应和副作用，未经证实的进行性疾病以及免疫抗性的复杂调控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，溶瘤病毒基因编辑时代的到来，以及mRNA疫苗和纳米递送系统技术障碍的突破，目前已经取得了显着的突破。本文从免疫检查点靶点的作用机制、ICB与肿瘤突变负荷的关系、关键的免疫调节或耐药信号通路、经典靶点和新靶点在不同肿瘤类型中有效性的具体临床证据等方面进行综述，并对药物安全性提出辩证思考。最后，我们讨论的重要性，准确分诊的ICB的基础上预测生物标志物和诊断检测技术的最新进展。
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.
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DOI：
10.1084/jem.176.2.327
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baixeras E;Huard B;Miossec C;Jitsukawa S;Martin M;Hercend T;Auffray C;Triebel F;Piatier-Tonneau D
通讯作者：
Piatier-Tonneau D
DOI：
10.4049/jimmunol.1402550
发表时间：
2015-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bally AP;Lu P;Tang Y;Austin JW;Scharer CD;Ahmed R;Boss JM
通讯作者：
Boss JM
影响因子：
8.7
作者：
Allard B;Longhi MS;Robson SC;Stagg J
通讯作者：
Stagg J
影响因子：
18.4
作者：
Böttcher JP;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
50.3
作者：
Alam, Hunain;Tang, Ming;Lee, Min Gyu
通讯作者：
Lee, Min Gyu