Kerr Keith M, Nicolson Marianne C
From the Department of Pathology, Aberdeen University School of Medicine (Dr Kerr), and the Department of Oncology (Dr Nicolson), Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
Arch Pathol Lab Med. 2016 Mar;140(3):249-54. doi: 10.5858/arpa.2015-0303-SA.
Although most primary cancers of the lung carry a heavy mutational load and will potentially present many "nonself" antigens to the immune system, there are a wide range of possible mechanisms for tumors to avoid so-called immune surveillance. One such mechanism is the adoption of immune checkpoints to inhibit the host immune response. Immune checkpoint inhibitors show great promise in the treatment of advanced non-small cell lung cancer.
To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti-PD-1 or anti-PD-L1 therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges.
Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used.
The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead.
尽管大多数原发性肺癌携带大量突变负荷，并可能向免疫系统呈现许多“非自身”抗原，但肿瘤有多种可能的机制来逃避所谓的免疫监视。其中一种机制是采用免疫检查点来抑制宿主免疫反应。免疫检查点抑制剂在晚期非小细胞肺癌的治疗中显示出巨大前景。
探讨为这些治疗选择患者生物标志物的可能性。这正成为一个备受争议的问题，抑制性程序性死亡受体1（PD-1）检查点的配体程序性死亡配体1（PD-L1）的免疫组化检测是一种可能的生物标志物。目前可得的数据显示出一些相互矛盾的结果，但PD-L1免疫组化似乎可能会被引入临床，用于选择接受抗PD-1或抗PD-L1治疗的患者。鉴于有4种此类药物即将迅速获得监管批准，每种药物都有其独立的PD-L1免疫组化生物标志物检测方法，肿瘤学家和病理学家都面临一些重大挑战。
使用了经过同行评审的文献和会议记录，尤其是过去12个月期间的。
PD-1/PD-L1的生物学特性复杂，这些药物的临床数据差异很大，PD-L1生物标志物检测的选择性能并不完美，4种药物/检测组合的存在显著增加了所面临的问题。本文阐述了这一治疗问题的一些背景，并讨论了未来的一些问题。
