PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance.
Head Neck
; 43(11): 3364-3373, 2021 11.
Article
in En
| MEDLINE
| ID: mdl-34346116
ABSTRACT
BACKGROUND:
Tumor models resistant to EGFR tyrosine kinase inhibitors or cisplatin express higher levels of the immune checkpoint molecule PD-L1. We sought to determine whether PD-L1 expression is elevated in head and neck squamous cell carcinoma (HNSCC) models of acquired cetuximab resistance and whether the expression is regulated by bromodomain and extraterminal domain (BET) proteins.METHODS:
Expression of PD-L1 was assessed in HNSCC cell line models of acquired cetuximab resistance. Proteolysis targeting chimera (PROTAC)- and RNAi-mediated targeting were used to assess the role of BET proteins.RESULTS:
Cetuximab-resistant HNSCC cells expressed elevated PD-L1 compared to cetuximab-sensitive controls. Treatment with the BET inhibitor JQ1, the BET PROTAC MZ1, or RNAi-mediated knockdown of BRD2 decreased PD-L1 expression. Knockdown of BRD2 also reduced the elevated levels of PD-L1 seen in a model of acquired cisplatin resistance.CONCLUSIONS:
PD-L1 is significantly elevated in HNSCC models of acquired cetuximab and cisplatin resistance where BRD2 is the primary regulator.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B7-H1 Antigen
/
Head and Neck Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Head Neck
Journal subject:
NEOPLASIAS
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos