Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.
Abstract
T cells in resistant patients, and nLSD1p regulates EOMES nuclear dynamics via demethylation/acetylation switching of critical EOMES residues. Using novel antibodies to target these post-translational modifications, we show that EOMES demethylation/acetylation is reciprocally expressed in resistant and responder patients. Overall, we show for the first time that dual inhibition of metastatic cancer cells and re-invigoration of the immune system requires LSD1 inhibitors that target the nLSD1p axis.
| Authors | Tu, Wen Juan; McCuaig, Robert D; Tan, Abel H Y; Hardy, Kristine; Seddiki, Nabila; Ali, Sayed; Dahlstrom, Jane E; Bean, Elaine G; Dunn, Jenny; Forwood, Jade; Tsimbalyuk, Sofia; Smith, Kate; Yip, Desmond; Malik, Laeeq; Prasanna, Thiru; Milburn, Peter; Rao, Sudha |
|---|---|
| Journal | Frontiers in Immunology |
| Pages | 1228 |
| Volume | 11 |
| Date | 1/06/2020 |
| Grant ID | APP1068065 |
| Funding Body | National Health and Medical Research Council |
| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.3389/fimmu.2020.01228 |