Zhou, ZhuolongVan der Jeught, KevinFang, YuanzhangYu, TaoLi, YujingAo, ZhengLiu, ShengZhang, LuYang, YangEyvani, HaniyehCox, Mary L.Wang, XiyuHe, XiaomingJi, GuangSchneider, Bryan P.Guo, FengWan, JunZhang, XinnaLu, Xiongbin2023-06-152023-06-152021Zhou Z, Van der Jeught K, Fang Y, et al. An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity. Nat Biomed Eng. 2021;5(11):1320-1335. doi:10.1038/s41551-021-00805-xhttps://hdl.handle.net/1805/33791In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers.en-USPublisher PolicyAntigen presentationBreast neoplasmsGenetic epigenesisOrganoidsArticle