Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti-PD-1 Resistance in Head and Neck Cancer.

ABSTRACT:

Purpose

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.

Experimental design

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-deficient cell lines were generated using CRISPR-CAS9. GSK126 and anti-PD-1-block

SUBMITTER: Zhou L 

PROVIDER: S-EPMC6942613 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature