Topalian Suzanne L, Taube Janis M, Anders Robert A, Pardoll Drew M
Department of Surgery, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
Department of Dermatology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, 1550 Orleans Street, CRB2 Room 508, Baltimore, Maryland 21287, USA.
Nat Rev Cancer. 2016 May;16(5):275-87. doi: 10.1038/nrc.2016.36. Epub 2016 Apr 15.
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.
随着多种治疗性抗体最近在黑色素瘤、非小细胞肺癌和肾癌中获批，这些抗体可阻断细胞毒性T淋巴细胞相关抗原4（CTLA4）和程序性细胞死亡蛋白1（PD1），并且临床上还有其他免疫检查点成为靶向目标，关于阻断这些检查点通路药物的最佳使用仍存在许多问题。定义预测治疗效果和不良事件的生物标志物是一项至关重要的任务，最近两种PDL1诊断测试的获批就凸显了这一点。在此，我们基于免疫学、遗传学和病毒学标准讨论抗PD1治疗的生物标志物。与PD1相比，CTLA4免疫检查点的独特生物学特性需要采用不同的生物标志物开发方法。此类研究基于机制的见解可能会指导基于免疫检查点阻断的协同治疗组合的设计。
