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

Autor: 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.
Jazyk: angličtina
Zdroj: Head & neck [Head Neck] 2021 Nov; Vol. 43 (11), pp. 3364-3373. Date of Electronic Publication: 2021 Aug 03.
DOI: 10.1002/hed.26827
Abstrakt: 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.)
Databáze: MEDLINE
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