美国德克萨斯大学安德森癌症中心Mien-Chie Hung小组取得一项新进展。他们的最新研究揭示去除糖基化可以提高PD-L1的检测，并预测抗PD-1/PD-L1的治疗效果。该项研究成果发表在2019年8月12日出版的《癌细胞》上。

因为PD-L1是高度糖基化的，研究人员开发了一种利用酶消化从细胞表面抗原中除去聚糖基团的方法来解决这个问题，该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，使PD-L1定量和预测临床结果更加准确。这项工作提出的PD-L1抗原修复方法可以提供一种实用且及时的方法来减少指导抗PD-1/PD-L1疗法的假阴性患者分类。

据悉，通过PD-1/PD-L1免疫检查点阻断来重新激活T细胞免疫已被证明是一种有希望的癌症治疗策略。然而，PD-L1免疫组化评估与患者反应不一致，这对患者的分类提出了临床挑战。
 

附：英文原文

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

Author: 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

Issue&Volume: Volume 36 Issue 2

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.

DOI: https://doi.org/10.1016/j.ccell.2019.06.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30299-5