预测生物标志物和抗 PD1/PD-L1 阻断癌症免疫治疗的机制。
Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy.
机构信息
NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, Hunan, China.
出版信息
Mol Cancer. 2020 Jan 30;19(1):19. doi: 10.1186/s12943-020-1144-6.
Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.
免疫检查点阻断针对 PD-1/PD-L1 在多种肿瘤中具有有前景的治疗效果，但治疗过程中的耐药性是一个主要问题。在这篇综述中，我们描述了 PD-L1 表达水平、突变负担、免疫细胞浸润和免疫细胞功能在预测 PD-1/PD-L1 阻断治疗疗效方面的应用。此外，我们探讨了肿瘤细胞上 PD-L1 表达、T 细胞功能障碍和 T 细胞耗竭导致免疫治疗耐药的机制。基于这些机制，我们提出了联合治疗策略。我们强调了制定个体化治疗计划的重要性，以降低经济负担并延长患者的生命。本综述中描述的预测指标、耐药机制和联合治疗为改善精准医学提供了基础。
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