CTLA4 promoter methylation predicts response and progression-free survival in stage IV melanoma treated with anti-CTLA-4 immunotherapy (ipilimumab).
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ therapeutic use
Biomarkers, Tumor
/ genetics
CTLA-4 Antigen
/ genetics
DNA Methylation
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Ipilimumab
/ therapeutic use
Male
Melanoma
/ drug therapy
Middle Aged
Prognosis
Promoter Regions, Genetic
Retrospective Studies
Survival Rate
CTLA-4
CTLA4
DNA methylation
Immunotherapy
Melanoma
Predictive biomarker
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
23
07
2020
accepted:
20
10
2020
pubmed:
17
11
2020
medline:
1
6
2021
entrez:
16
11
2020
Statut:
ppublish
Résumé
Anti-CTLA-4-antibodies can induce long-lasting tumor remissions. However, only a few patients respond, necessitating the development of predictive companion biomarkers. Increasing evidence suggests a major role of epigenetics, including DNA methylation, in immunology and resistance to immune checkpoint blockade. Here, we tested CTLA4 promoter methylation and CTLA-4 protein expression as predictive biomarkers for response to anti-CTLA-4 immunotherapy. We identified retrospectively N = 30 stage IV melanoma patients treated with single-agent anti-CTLA-4 immunotherapy (ipilimumab). We used quantitative methylation-specific PCR and immunohistochemistry to quantify CTLA4 methylation and protein expression in pre-treatment samples. CTLA4 methylation was significantly higher in progressive as compared to responding tumors and significantly associated with progression-free survival. A subset of infiltrating lymphocytes and tumor cells highly expressed CTLA-4. However, CTLA-4 protein expression did not predict response to treatment. We conclude that CTLA4 methylation is a predictive biomarker for response to anti-CTLA-4 immunotherapy.
Identifiants
pubmed: 33196890
doi: 10.1007/s00262-020-02777-4
pii: 10.1007/s00262-020-02777-4
pmc: PMC8139923
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
Ipilimumab
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1781-1788Subventions
Organisme : BONFOR program of the University Hospital Bonn
ID : O-105.0069
Organisme : DFG Cluster of Excellence ImmunoSensation
ID : EXC 1023
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