Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy (Cancer Cell 2019, 36(2):168-178.)

報告日期: 2019/10/04
報告時間: 15:10/16:00
報告學生: 黃翊庭
講評老師: 張權發
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Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1/PD-L1 therapeutic efficacy

Heng-Huan Lee. et al. Cancer Cells. (2019) 36:1-11.

Speaker: Yi-Ting Huang (黃翊庭)                  Time: 15:00-16:00, Oct. 04, 2019                          

Commentator: Dr. Chuan-Fa Chang (張權發老師)           Place: Room 602

Abstract:

The field of immunotherapy has dramatically reshaped the landscape of cancer therapy since the development of immune checkpoint blockade. Reactivation of T cell immunity by PD-1/PD-L1 immune checkpoint blockade has been shown to be a promising cancer therapeutic strategy. Antibodies specifically targeting PD-1 or PD-L1 have been approved by FDA for second and even first-line treatment against various cancer types. However, accumulating evidence from both preclinical and clinical studies indicates that the pathological assessment of PD-L1 levels in patients’ cancer tissues is neither a consistent nor reliable predictor of anti-PD-1/PD-L1 therapy outcomes these years. Some recent studies showed that in the majority of cells in which it is expressed, PD-L1 is highly glycosylated with heterogeneous expression patterns on Western blots. Moreover, N-linked glycosylation is a biosynthetic secretory pathway in the endoplasmic reticulum and Golgi apparatus. In this study, the authors 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 in various types of cancer cell lines. In addition to this, the authors also found that removing the glycan moieties from tumor samples before IHC staining leads to a more accurate assessment of PD-L1 expression to allow better prediction of clinical response to anti-PD-1/PD-L1 therapy. Concluding these cellular, IHC and pre-clinical results, these data suggested that removal of the glycan moiety of PD-L1 enhances its detection by IHC using antibodies that recognize PD-L1 polypeptide and 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.

References:

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