PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance.

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Tytuł:: PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance.
Autorzy:: Bhola NE; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Njatcha C; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Hu L; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Lee ED; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Shiah JV; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Kim MO; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Johnson DE; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Grandis JR; Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.
Źródło:: Head & neck [Head Neck] 2021 Nov; Vol. 43 (11), pp. 3364-3373. Date of Electronic Publication: 2021 Aug 03.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Publication: New York, NY : John Wiley And Sons
Original Publication: New York, NY : J. Wiley, c1989-
MeSH Terms:: B7-H1 Antigen*/genetics
Head and Neck Neoplasms*/drug therapy
Head and Neck Neoplasms*/genetics
Cell Line, Tumor ; Cetuximab/pharmacology ; Drug Resistance, Neoplasm/genetics ; Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/genetics ; Transcription Factors
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Grant Information:: U54 CA209891 United States CA NCI NIH HHS; R35 CA231998 United States CA NCI NIH HHS; T32 DE007306 United States DE NIDCR NIH HHS
Contributed Indexing:: Keywords: BET; BRD2; PD-L1 upregulation; cetuximab resistance
Substance Nomenclature:: 0 (B7-H1 Antigen)
0 (BRD2 protein, human)
0 (CD274 protein, human)
0 (Transcription Factors)
PQX0D8J21J (Cetuximab)
Entry Date(s):: Date Created: 20210804 Date Completed: 20211028 Latest Revision: 20220531
Update Code:: 20240105
PubMed Central ID:: PMC8664160
DOI:: 10.1002/hed.26827
PMID:: 34346116
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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.
(© 2021 Wiley Periodicals LLC.)

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