Evidence map›Paper›PMID 33073996›Full record

ArticleJournal of proteome research2021

PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.

Julius Benicky, Miloslav Sanda, Zuzana Brnakova Kennedy, Oliver C Grant, Robert J Woods, Alan Zwart, Radoslav Goldman

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 54 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Julius BenickyDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, United States.
Miloslav SandaDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, United States.ORCID 0000-0002-7735-3635
Zuzana Brnakova KennedyDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, United States.
Oliver C GrantDepartment of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
Robert J WoodsDepartment of Biochemistry and Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0002-2400-6293
Alan ZwartDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, United States.
Radoslav GoldmanDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C. 20057, United States.ORCID 0000-0003-1304-0522
Georgetown University · USUniversity of Georgia · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
Glycans in Hepatocellular CarcinomaR01CA135069 · NCI · GEORGETOWN UNIVERSITY · PI GOLDMAN, RADOSLAV · 2009 to 2019
$4.1M
O-glycoproteins in the progression of liver diseaseR01CA238455 · NCI · GEORGETOWN UNIVERSITY · PI GOLDMAN, RADOSLAV · 2019 to 2023
$2.6M
Alliance of Glycobiologists for Detection of CancerU01CA168926 · NCI · GEORGETOWN UNIVERSITY · PI GOLDMAN, RADOSLAV · 2012 to 2016
$2.0M
Tools to enable non-specialists to model glycoconjugates and glycan-protein interactionsU01CA207824 · NCI · UNIVERSITY OF GEORGIA · PI FOLEY, B. LACHELE, WOODS, ROBERT J · 2016 to 2018
$1.7M
LC-MS Analysis of Site Specific Protein GlycoformsU01CA230692 · NCI · GEORGETOWN UNIVERSITY · PI EDWARDS, NATHAN J, GOLDMAN, RADOSLAV · 2018 to 2020
$1.3M
Orbitrap Fusion Lumos ETDS10OD023557 · OD · GEORGETOWN UNIVERSITY · PI GOLDMAN, RADOSLAV · 2017 to 2017
$1.1M
NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA135069NCI NIH HHS R01 CA238455NCI NIH HHS U01 CA168926NCI NIH HHS U01 CA207824NCI NIH HHS U01 CA230692NIGMS NIH HHS P41 GM103390NIH HHS S10 OD023557
6 · The paper itself

Abstract

Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of the immune response and promising targets in cancer immunotherapy. N-glycosylation of PD-L1 affects its interaction with PD-1, but little is known about the distribution of glycoforms at its four NXS/T sequons. We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs. We demonstrate that PD-L1 on the surface of breast cancer cell line carries mostly complex glycans with a high proportion of polyLacNAc structures at the N219 sequon. Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures. Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 may be involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown. The interaction of PD-L1 with clinical antibodies is also affected by glycosylation. In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cell line carries polyLacNAc glycans mostly at the N219 sequon, which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.

Indexed as

B7-H1 AntigenTandem Mass SpectrometryChromatography, LiquidGlycosylationHEK293 CellsHumansB7-H1 Antigenbinding constantdurvalumabimmune checkpointsN-glycosylationPD-L1polyLacNAcprogrammed cell death ligand-1site-specific glycosylationsurface plasmon resonancetherapeutic antibody

Identifiers

PMID33073996
PMCPMC8158060
OpenAlexW3092652519

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.