Cancer Cell
Volume 36, Issue 2, 12 August 2019, Pages 168-178.e4
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Article
Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy

https://doi.org/10.1016/j.ccell.2019.06.008Get rights and content
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Highlights

  • N-linked glycosylation of PD-L1 hinders its recognition by PD-L1 antibodies

  • Removal of glycosylation enhances anti-PD-L1 signal in a variety of bioassays

  • Patient sample deglycosylation prevents false-negative detection of PD-L1

  • Deglycosylated PD-L1 is a more reliable biomarker to guide immunotherapy

Summary

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.

Keywords

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

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These authors contributed equally

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