Lee and Wang et al. demonstrated that enzymatic removal of N-linked glycans from PD-L1 on the surface of tumor cells in patient samples significantly improved PD-L1 binding affinity and signal intensity in a variety of assays commonly used to stratify patients for cancer immunotherapy. After sample deglycosylation, improved PD-L1 detection was observed in different types of cancers and positively correlated with PFS and OS after anti-PD-1/PD-L1 therapy. The enhanced PD-L1 signal decreased the false negatives and underdetection of PD-L1, significantly increasing the fraction of patients eligible for anti-PD-1/PD-L1 therapy.
Contributed by Katherine Turner
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.
Author Info: (1) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (2) Department of Molecular and Cellular Oncology, The
Author Info: (1) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (2) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (3) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (4) Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan. (5) Department of Hematology-Oncology, E-Da Cancer Hospital, Kaohsiung 824, Taiwan; Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaoshiung 833, Taiwan. (6) Department of Pulmonary Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China. (7) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (8) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (9) Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan. (10) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Pathology, Harbin Medical University, Harbin, Heilongjiang 150081, China. (11) Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan. (12) Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan. (13) Cancer Center, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. (14) Cancer Center, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. (15) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (16) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan. (17) Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. (18) Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan; Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: mhung@mail.cmu.edu.tw.
