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

Heng Huan Lee, Ying Nai Wang, W. Xia, Chia Hung Chen, Kun Ming Rau, Leiguang Ye, Yongkun Wei, Chao Kai Chou, Shao Chun Wang, M. 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

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

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. Histological detection of PD-L1 may guide therapy with anti-PD-1/PD-L1 antibodies but some PD-L1-negative tumors respond to these treatments. Lee et al. show that enzymatic deglycosylation of tissue sections improves PD-L1 detection and its predictive value, and could potentially impact patient stratification.

Original languageEnglish (US)
Pages (from-to)168-178.e4
JournalCancer cell
Volume36
Issue number2
DOIs
StatePublished - Aug 12 2019

Keywords

  • PD-1
  • PD-L1
  • antibody-based detection
  • biomarker
  • glycosylation/deglycosylation
  • heterogeneity/homogeneity
  • immune checkpoint
  • immunohistochemistry
  • immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core
  • Functional Genomics Core
  • Tissue Biospecimen and Pathology Resource
  • Cytogenetics and Cell Authentication Core

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