Deglycosylated PD-L1 is a biomarker for immune checkpoint blockade response: a real-world study in breast cancer patients in Taiwan

Abstract

Triple-negative breast cancer (TNBC) is characterized by limited therapeutic options and a generally poor prognosis. Immune checkpoint blockade (ICB) therapies, particularly those targeting the PD-1/PD-L1 axis, offer promising treatment avenues, yet their effectiveness is contingent upon accurate assessment of PD-L1 expression. In this study, we collected 154 archived ICB-naïve TNBC tumor samples from multiple hospitals across Taiwan. We used immunohistochemistry (IHC) staining with the 28-8 monoclonal antibody to compare PD-L1 detection in samples treated with and without deglycosylation. Our findings revealed that under the standard IHC protocol without deglycosylation, 33.12 % of TNBC samples were classified as PD-L1 negative, which would have excluded these patients from ICB therapy eligibility. After deglycosylation, 84.31 % of the initially PD-L1-negative cases were reclassified as PD-L1 positive, indicating that glycosylation led to a 27.92 % false-negative rate in the TNBC samples. Notably, higher PD-L1 levels post-de-glycosylation were significantly associated with favorable responses to ICB treatments, particularly among patients receiving pembrolizumab and atezolizumab. Receiver operating characteristic (ROC) analysis demonstrated a stronger correlation between deglycosylated PD-L1 and treatment response, with an area under the curve (AUC) of 0.860, compared to 0.648 for non-deglycosylated PD-L1. These results underscore the clinical importance of deglycosylation in enhancing PD-L1 detection accuracy, enabling more precise patient selection for ICB therapies. Incorporating deglycosylation into PD-L1 assessment protocols may improve treatment outcomes for TNBC patients and establish deglycosylated PD-L1 as a more reliable biomarker for ICB therapy response.

Keywords: Atezolizumab; Biomarker; Glycosylation; PD-L1; Pembrolizumab; Triple-negative breast cancer.