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

被引：323

作者：

Lee, Heng-Huan ^{[1
]}

Wang, Ying-Nai ^{[1
]}

Xia, Weiya ^{[1
]}

Chen, Chia-Hung ^{[2
,3
]}

Rau, Kun-Ming ^{[4
,5
]}

Ye, Leiguang ^{[6
]}

Wei, Yongkun ^{[1
]}

Chou, Chao-Kai ^{[1
]}

Wang, Shao-Chun ^{[7
,8
]}

Yan, Meisi ^{[1
,9
]}

Tu, Chih-Yen ^{[2
,3
]}

Hsia, Te-Chun ^{[2
,3
]}

Chiang, Shu-Fen ^{[10
]}

Chao, K. S. Clifford ^{[10
]}

Wistuba, Ignacio I. ^{[11
]}

Hsu, Jennifer L. ^{[1
,7
,8
,12
]}

Hortobagyi, Gabriel N. ^{[13
]}

Hung, Mien-Chie ^{[1
,7
,8
,12
,14
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[2] China Med Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Taichung 404, Taiwan

[3] China Med Univ, Sch Med, Taichung 404, Taiwan

[4] E Da Canc Hosp, Dept Hematol Oncol, Kaohsiung 824, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Div Hematol Oncol, Kaohsiung 833, Taiwan

[6] Harbin Med Univ, Affiliated Tumor Hosp, Dept Pulm Oncol, Harbin 150081, Heilongjiang, Peoples R China

[7] China Med Univ, Grad Inst Biomed Sci, Taichung 404, Taiwan

[8] China Med Univ, Ctr Mol Med, Taichung 404, Taiwan

[9] Harbin Med Univ, Dept Pathol, Harbin 150081, Heilongjiang, Peoples R China

[10] China Med Univ, China Med Univ Hosp, Canc Ctr, Taichung 404, Taiwan

[11] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[12] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan

[13] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[14] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA

来源：

CANCER CELL | 2019年 / 36卷 / 02期

关键词：

CELL LUNG-CANCER; TUMOR-INFILTRATING LYMPHOCYTES; IMMUNE-CHECKPOINT BLOCKADE; PROGRAMMED DEATH LIGAND-1; STANDARDIZED METHOD; MASS-SPECTROMETRY; SOLID TUMORS; OPEN-LABEL; DOCETAXEL; BIOMARKERS;

D O I：

10.1016/j.ccell.2019.06.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：168 / +

页数：15

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