gsk-2816126 has been researched along with Head-and-Neck-Neoplasms* in 1 studies
1 other study(ies) available for gsk-2816126 and Head-and-Neck-Neoplasms
| Article | Year |
|---|---|
Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer.
Anti-programmed death-1 (PD-1) receptor-based therapeutics improve survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC), but many do not benefit due to a low response rate. Herein, we identified EZH2 as a therapeutic target that enhanced tumor cell antigen presentation and subsequently sensitized resistant tumors to anti-PD-1 therapy.. EZH2 regulation of antigen presentation was defined using EZH2 inhibitors (GSK126 and EPZ6438) in human and mouse HNSCC cell lines. Mechanistic dissection of EZH2 in regulation of antigen presentation was investigated using flow cytometry, qRT-PCR, ELISA, and chromatin-immunoprecipitation assays.. EZH2 expression was negatively correlated with antigen-processing machinery pathway components in HNSCC data sets in The Cancer Genome Atlas. EZH2 inhibition resulted in significant upregulation of MHC class I expression in human and mouse human papillomavirus-negative HNSCC lines. Our results demonstrated that targeting EZH2 enhanced antigen presentation and was able to circumvent anti-PD-1 resistance. Thus, combining EZH2 targeting with anti-PD-1 may increase therapeutic susceptibility in HNSCC. Topics: Animals; Antigen Presentation; Antineoplastic Agents, Immunological; Benzamides; Biphenyl Compounds; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Drug Resistance, Neoplasm; Enhancer of Zeste Homolog 2 Protein; Female; Head and Neck Neoplasms; Humans; Immunity, Cellular; Indoles; Mice; Mice, Inbred C57BL; Morpholines; Programmed Cell Death 1 Receptor; Pyridones | 2020 |