Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy
Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy
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DOI：
10.1016/j.ccell.2019.06.008
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发表时间：
2019-08-12
期刊：
影响因子：
50.3
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
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作者：
Lee, Heng-Huan;Wang, Ying-Nai;Hung, Mien-Chie
通过PD-1/PD-L1免疫检查点阻断重新激活T细胞免疫已被证明是一种有前途的癌症治疗策略。然而，PD-L1免疫组化读数与患者反应不一致，这对患者分层提出了临床挑战。由于PD-L1是高度糖基化的，我们开发了一种方法来解决这个问题，通过酶消化从细胞表面抗原中去除聚糖部分，这一过程称为样品去糖基化。值得注意的是，去糖基化显著改善了抗PD-L1抗体结合亲和力和信号强度，导致更准确的PD-L1定量和临床结果预测。这种提出的PD-L1抗原修复方法可能提供一种实用和及时的方法，以减少假阴性患者分层，从而指导抗PD-1/PD-L1治疗。
Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. However, PD-L1 immunohistochemical readout is inconsistent with patient response, which presents a clinical challenge to stratify patients. Because PD-L1 is heavily glycosylated, we developed a method to resolve this by removing the glycan moieties from cell surface antigens via enzymatic digestion, a process termed sample deglycosylation. Notably, deglycosylation significantly improves anti-PD-L1 antibody binding affinity and signal intensity, resulting in more accurate PD-L1 quantification and prediction of clinical outcome. This proposed method of PD-L1 antigen retrieval may provide a practical and timely approach to reduce false-negative patient stratification for guiding anti-PD-1/PD-L1 therapy.