Journal
CANCER CELL
Volume 36, Issue 2, Pages 168-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.06.008
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Funding
- Ruth Leggett Distinguished Chair Endowment
- MDA Startup Fund
- University of Texas MD Anderson-China Medical University, Taiwan and Hospital Sister Institution Fund
- Breast Cancer Research Foundation [BCRF-17-069]
- Cancer Prevention and Research Institute of Texas [RP160710]
- T32 Training Grant in Cancer Biology [5T32CA186892]
- Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence [MOHW108-TDU-B-212-124024, MOHW108-TDU-B-212-122015]
- Drug Development Center, China Medical University from the Featured Areas Research Center Program by Ministry of Education
- Cancer Center (NIH) [P30 CA016672]
- Center for Biological Pathways
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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.
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