Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy

去除N-连接糖基化可增强PD-L1的检测并预测抗PD-1/PD-L1疗法的疗效

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作者:Heng-Huan Lee ,Ying-Nai Wang ,Weiya Xia ,Chia-Hung Chen ,Kun-Ming Rau ,Leiguang Ye ,Yongkun Wei ,Chao-Kai Chou ,Shao-Chun Wang ,Meisi Yan ,Chih-Yen Tu ,Te-Chun Hsia ,Shu-Fen Chiang ,K S Clifford Chao ,Ignacio I Wistuba ,Jennifer L Hsu ,Gabriel N Hortobagyi ,Mien-Chie Hung

Abstract

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.

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