MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series.
Aged
Aged, 80 and over
Antibodies, Monoclonal
/ immunology
B7-H1 Antigen
/ antagonists & inhibitors
Carcinoma, Merkel Cell
/ drug therapy
Down-Regulation
/ drug effects
Drug Resistance, Neoplasm
/ drug effects
Female
Histocompatibility Antigens Class I
/ genetics
Histone Deacetylase Inhibitors
/ immunology
Humans
Immunotherapy
/ methods
Male
Middle Aged
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Skin Neoplasms
/ drug therapy
HDAC inhibitor
HLA class-I
Immunotherapy
Infiltration
Merkel cell carcinoma
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 2019
Jun 2019
Historique:
received:
10
09
2018
accepted:
11
04
2019
pubmed:
18
4
2019
medline:
4
6
2019
entrez:
18
4
2019
Statut:
ppublish
Résumé
Merkel cell carcinoma (MCC) is an aggressive skin cancer in which PD-1/PD-L1 blockade has shown remarkable response rates. However, a significant proportion of patients shows primary or secondary resistance against PD-1/PD-L1 inhibition, with HLA class-I downregulation and insufficient influx of CD8 We report four cases of patients with metastatic MCC who did not respond to immunotherapy by PD-1/PD-L1 blockade. Two of the patients received, subsequently, the HDACi panobinostat in combination with PD-1/PD-L1 blockade. Tumor biopsies of the patients were analyzed for cellular and molecular markers of antigen processing and presentation as well as the degree of T-cell infiltration. Low expression of APM-related genes associated with low HLA class-I surface expression was observed in all MCC patients, progressing on PD-1/PD-L1 blockade. In one evaluable patient, of the two treated with the combination therapy of the HDACi, panobinostat and PD-1/PD-L1 blockade, reintroduction of HLA class-I-related genes, enhanced HLA class-I surface expression, and elevated CD8
Sections du résumé
BACKGROUND
BACKGROUND
Merkel cell carcinoma (MCC) is an aggressive skin cancer in which PD-1/PD-L1 blockade has shown remarkable response rates. However, a significant proportion of patients shows primary or secondary resistance against PD-1/PD-L1 inhibition, with HLA class-I downregulation and insufficient influx of CD8
CASE PRESENTATIONS
METHODS
We report four cases of patients with metastatic MCC who did not respond to immunotherapy by PD-1/PD-L1 blockade. Two of the patients received, subsequently, the HDACi panobinostat in combination with PD-1/PD-L1 blockade. Tumor biopsies of the patients were analyzed for cellular and molecular markers of antigen processing and presentation as well as the degree of T-cell infiltration.
RESULTS AND CONCLUSION
CONCLUSIONS
Low expression of APM-related genes associated with low HLA class-I surface expression was observed in all MCC patients, progressing on PD-1/PD-L1 blockade. In one evaluable patient, of the two treated with the combination therapy of the HDACi, panobinostat and PD-1/PD-L1 blockade, reintroduction of HLA class-I-related genes, enhanced HLA class-I surface expression, and elevated CD8
Identifiants
pubmed: 30993371
doi: 10.1007/s00262-019-02341-9
pii: 10.1007/s00262-019-02341-9
doi:
Substances chimiques
Antibodies, Monoclonal
0
B7-H1 Antigen
0
Histocompatibility Antigens Class I
0
Histone Deacetylase Inhibitors
0
Programmed Cell Death 1 Receptor
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM