Haanen John B A G, Thienen Hans van, Blank Christian U
Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Semin Oncol. 2015 Jun;42(3):423-8. doi: 10.1053/j.seminoncol.2015.02.011. Epub 2015 Feb 14.
Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation of peripheral tolerance in order to prevent autoimmunity. Blocking of these cell surface proteins by antibodies has resulted in remarkable anti-tumor immunity; however this immunity is accompanied by immune-related adverse reactions (irAEs), resembling autoimmune diseases. Hence, treatment with immunosuppressive drugs is highly effective and resolves the symptoms caused by these adverse events rapidly. In this review, toxicity patterns observed with immune checkpoint blockade are described for single-agent and combination treatments.
免疫检查点分子细胞毒性T淋巴细胞抗原4（CTLA-4）、程序性死亡1（PD-1）以及淋巴细胞活化基因3（LAG-3）和T细胞免疫球蛋白黏蛋白分子3（TIM-3）都参与外周耐受的调节，以预防自身免疫。用抗体阻断这些细胞表面蛋白可产生显著的抗肿瘤免疫；然而，这种免疫会伴有免疫相关不良反应（irAE），类似于自身免疫性疾病。因此，使用免疫抑制药物进行治疗非常有效，能迅速缓解这些不良事件引起的症状。在本综述中，描述了单药治疗和联合治疗中观察到的免疫检查点阻断毒性模式。
