An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity
dc.contributor.author | Zhou, Zhuolong | |
dc.contributor.author | Van der Jeught, Kevin | |
dc.contributor.author | Fang, Yuanzhang | |
dc.contributor.author | Yu, Tao | |
dc.contributor.author | Li, Yujing | |
dc.contributor.author | Ao, Zheng | |
dc.contributor.author | Liu, Sheng | |
dc.contributor.author | Zhang, Lu | |
dc.contributor.author | Yang, Yang | |
dc.contributor.author | Eyvani, Haniyeh | |
dc.contributor.author | Cox, Mary L. | |
dc.contributor.author | Wang, Xiyu | |
dc.contributor.author | He, Xiaoming | |
dc.contributor.author | Ji, Guang | |
dc.contributor.author | Schneider, Bryan P. | |
dc.contributor.author | Guo, Feng | |
dc.contributor.author | Wan, Jun | |
dc.contributor.author | Zhang, Xinna | |
dc.contributor.author | Lu, Xiongbin | |
dc.contributor.department | Medical and Molecular Genetics, School of Medicine | en_US |
dc.date.accessioned | 2023-06-15T16:43:20Z | |
dc.date.available | 2023-06-15T16:43:20Z | |
dc.date.issued | 2021 | |
dc.description.abstract | In 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_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Zhou 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-x | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/33791 | |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isversionof | 10.1038/s41551-021-00805-x | en_US |
dc.relation.journal | Nature Biomedical Engineering | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Antigen presentation | en_US |
dc.subject | Breast neoplasms | en_US |
dc.subject | Genetic epigenesis | en_US |
dc.subject | Organoids | en_US |
dc.title | An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity | en_US |
dc.type | Article | en_US |