4.4 Article

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

Journal

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/15330338211019442

Keywords

biomarkers; DNA mismatch repair; gene expression; immune checkpoint inhibitors; immunotherapy

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Funding

  1. Natural Science Foundation of Jiangsu Province of China [BK20171150]
  2. Clinical Research Center Fund from Wuxi Science and Technology Bureau [WX18IVJN017]
  3. Key Speciality from Wuxi Health and Family Planning Commission [JZYX04]

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The removal of N-linked glycosylation significantly enhances PD-L1 detection accuracy. PD-L1 expression is significantly higher in colon cancer tissues compared to normal tissues, especially in colon tumors with defective mismatch repair. Improved stratification strategy for anti-PD-1/PD-L1 therapy in colon cancer has been provided by this study.
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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