Removal of N-Linked Glycosylation Enhances PD-L1 Detection in Colon Cancer: Validation Research Based on Immunohistochemistry Analysis

去除 N 连接糖基化可增强结肠癌中的 PD-L1 检测:基于免疫组织化学分析的验证研究

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作者:Junying Xu, Xuejing Yang, Yong Mao, Jie Mei, Huiyu Wang, Junli Ding, Dong Hua

Abstract

In recent years, immunotherapies have emerged as effective therapeutic strategies for treating human cancers. However, accumulating evidence has revealed an inconsistency between the response to immune checkpoint inhibitors and programmed death ligand 1 (PD-L1) expression status detected by immunohistochemistry staining. Recent research has revealed that the removal of N-Linked glycosylation significantly enhanced PD-L1 detection, resulting in both more accurate PD-L1 quantification and clinical outcome prediction. In the present study, we evaluated natural and deglycosylated PD-L1 expression in colon cancer using the PD-L1 28-8 antibody. The results of the present study validated the hypothesis that PD-L1 had a higher expression in colon cancer tissues compared with normal tissues. Additionally, colon tumors with defective mismatch repair tended to express higher PD-L1 than those without. Most importantly, the results of the present study indicated that the removal of N-linked glycosylation remarkably enhanced PD-L1 detection. Moreover, the PD-L1 signal intensity of samples with a low natural PD-L1 signal was enhanced more remarkably than that of samples with high signal intensity. Overall, our research provides an improved strategy for patient stratification for anti-PD-1/PD-L1 therapy, which deepens the clinical significance of this established strategy for treatment of colon cancer.

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