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肺癌免疫检查点治疗:现状与未来前景。

Targeting Immune Checkpoints in Lung Cancer: Current Landscape and Future Prospects.

机构信息

Department of Pathology, School of Basic Medical Science, Wuhan University, 185 Donghu Road, Medical Building 8, 10th Floor, Wuchang District, Wuhan, 430071, Hubei, People's Republic of China.

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.

出版信息

Clin Drug Investig. 2019 Apr;39(4):341-353. doi: 10.1007/s40261-018-00746-5.

Abstract

Lung cancer is the most prevalent and deadly cancer worldwide. Immune checkpoint therapy, which targets regulatory pathways in T cells to boost anti-tumor immune response, has revolutionized lung cancer treatment paradigms. Inhibitors of the most established immune checkpoints such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) have been approved by the US Food and Drug Administration in the management of lung cancer. Despite the pronounced survival benefits that have been seen with immune checkpoint inhibitors, not all lung cancer patients respond to single-agent immunotherapy due to the complexity of the immune microenvironment and tumor resistance. Alternative immune checkpoints beyond PD-1/PD-L1 must be sought so that more patients can benefit from immune checkpoint therapy. Additionally, novel combination strategies of immunotherapy and conventional treatments (e.g., chemotherapy, radiotherapy, and targeted therapy) have shown promise in some clinical trials. Meanwhile, identification of predictive biomarkers is pivotal in selecting eligible patients for immunotherapy and to guide individualized clinical decision-making. The future of immune checkpoint therapy in lung cancer is not devoid of challenges, and more prospective clinical studies are awaited to translate our understanding from bench to bedside.

摘要

肺癌是全球最普遍和最致命的癌症。免疫检查点疗法通过靶向 T 细胞的调节途径来增强抗肿瘤免疫反应,彻底改变了肺癌的治疗模式。美国食品和药物管理局已批准针对最成熟的免疫检查点(如程序性死亡受体 1[PD-1]/程序性死亡受体配体 1[PD-L1])的抑制剂用于肺癌的治疗。尽管免疫检查点抑制剂已显示出显著的生存获益,但并非所有肺癌患者对单药免疫治疗都有反应,这是由于免疫微环境和肿瘤耐药的复杂性所致。必须寻求除 PD-1/PD-L1 之外的其他替代免疫检查点,以使更多的患者能够从免疫检查点治疗中获益。此外,免疫治疗与传统治疗(如化疗、放疗和靶向治疗)的新联合策略在一些临床试验中显示出了希望。同时,鉴定预测性生物标志物对于选择适合免疫治疗的患者以及指导个体化临床决策至关重要。免疫检查点疗法在肺癌中的未来并非没有挑战,需要更多的前瞻性临床研究将我们从实验室的理解转化为临床实践。

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