PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer.

PD-L1 Testing in Guiding Patient Selection for PD-1/PD-L1 Inhibitor Therapy in Lung Cancer.
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PD-L1在指导患者选择PD-1/PD-L1抑制剂治疗中的PD-L1测试。

DOI:
10.1007/s40291-017-0308-6
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发表时间:
2018-03
影响因子:
4
通讯作者:
Villaruz LC
Villaruz LC
中科院分区:
医学3区
文献类型:
--
作者:
Ancevski Hunter K;Socinski MA;Villaruz LC

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使用程序性死亡1(PD-1)和程序性死亡配体1(PD-L1)靶向单克隆抗体的免疫疗法已经显著改变了几种类型的恶性肿瘤的治疗和预后前景。PD-1和PD-L1是免疫检查点蛋白,其结合最终导致T细胞耗竭和自身耐受。阻断这一途径可以“释放免疫系统的断裂”,并允许攻击表达PD-L1的肿瘤细胞。导致美国食品药品监督管理局(FDA)批准这些药物的临床试验使用不同的免疫组织化学(IHC)平台与各种PD-L1抗体来评估肿瘤细胞或肿瘤浸润免疫细胞上的PD-L1表达。FDA注册了四种PD-L1 IHC检测试剂盒,使用四种不同的PD-L1抗体(22 C3、28-8、SP263、SP142),在两种不同的IHC平台(Dako和Ventana)上进行检测,每种平台都有自己的评分系统。正在尝试协调PD-L1 IHC抗体和染色平台。虽然PD-L1 IHC可用于预测抗PD-1或抗PD-L1治疗的应答可能性,但一定比例的阴性患者可能具有应答,并且替代生物标志物的鉴定对于进一步完善最有可能对这些治疗应答的患者的选择至关重要。
Immunotherapy with programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) targeted monoclonal antibodies has dramatically changed the therapeutic and prognostic landscape for several types of malignancy. PD-1 and PD-L1 are immune checkpoint proteins whose binding ultimately result in T cell exhaustion and self-tolerance. Blocking this pathway “releases the breaks” on the immune system and allows for attack of tumor cells that express PD-L1. The clinical trials that led to The Food and Drug Administration (FDA) approval of these agents used different immunohistochemical (IHC) platforms with various PD-L1 antibodies to assess for PD-L1 expression on either tumor cells or tumor-infiltrating immune cells. There are four PD-L1 IHC assays registered with the FDA, using four different PD-L1 antibodies (22C3, 28–8, SP263, SP142), on two different IHC platforms (Dako and Ventana), each with their own scoring systems. Attempts at harmonization of PD-L1 IHC antibodies and staining platforms are underway. While PD-L1 IHC can be used to predict likelihood of response to anti-PD-1 or anti-PD-L1 therapy, a proportion of patients that are negative can have response and identification of alternative biomarkers is critical to further refine selection of patients most likely to respond to these therapies.
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