Topalian Suzanne L, Drake Charles G, Pardoll Drew M
Department of Surgery, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
The Brady Urological Institute, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Cancer Cell. 2015 Apr 13;27(4):450-61. doi: 10.1016/j.ccell.2015.03.001. Epub 2015 Apr 6.
The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study.
免疫系统能够识别并准备好清除癌症，但却受到抑制性受体和配体的制约。这些免疫检查点通路通常在抗微生物免疫反应期间维持自身耐受性并限制附带的组织损伤，癌症却可利用它们来逃避免疫破坏。阻断免疫检查点的药物，如抗CTLA-4、抗PD-1、抗PD-L1以及其他处于早期研发阶段的药物，能够释放抗肿瘤免疫力并介导持久的癌症消退。免疫检查点通路的复杂生物学特性仍存在许多谜团，目前，单独或联合使用检查点阻断药物的全部活性谱是深入研究的主题。
