A PD-1/PD-L1 Proximity Assay as a Theranostic Marker for PD-1 Blockade in Patients with Metastatic Melanoma.
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
B7-H1 Antigen
/ analysis
Biomarkers, Tumor
/ analysis
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Ipilimumab
/ administration & dosage
Melanoma
/ diagnosis
Nivolumab
/ administration & dosage
Programmed Cell Death 1 Receptor
/ analysis
Progression-Free Survival
Treatment Outcome
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
12
04
2021
revised:
06
07
2021
accepted:
08
11
2021
pubmed:
18
11
2021
medline:
23
3
2022
entrez:
17
11
2021
Statut:
ppublish
Résumé
Less than 50% of patients with melanoma respond to anti-programmed cell death protein 1 (anti-PD-1), and this treatment can induce severe toxicity. Predictive markers are thus needed to improve the benefit/risk ratio of immune checkpoint inhibitors (ICI). Baseline tumor parameters such as programmed death ligand 1 (PD-L1) expression, CD8 PD-1/PD-L1 proximity was assessed by proximity ligation assay (PLA) on 137 samples from two cohorts (exploratory A PD-1/PD-L1 PLA model was developed to predict tumor response in an exploratory cohort and further evaluated in an independent validation cohort. This score showed higher predictive ability (AUC = 0.85 and 0.79 in the two cohorts, respectively) for PD-1/PD-L1 PLA as compared with other parameters (AUC = 0.71-0.77). Progression-free and overall survival were significantly longer in patients with high PLA values ( The proximity between PD-1 and PD-L1, easily assessed by this PLA on one formalin-fixed paraffin-embedded section, appears as a new biomarker of anti-PD-1 efficacy.
Identifiants
pubmed: 34785583
pii: 1078-0432.CCR-21-1229
doi: 10.1158/1078-0432.CCR-21-1229
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
Ipilimumab
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
518-525Informations de copyright
©2021 American Association for Cancer Research.
Références
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