dc.contributor.author | Singer, Meromit | |
dc.contributor.author | Cong, Le | |
dc.contributor.author | Kowalczyk, Monika S. | |
dc.contributor.author | Zhang, Huiyuan | |
dc.contributor.author | Nyman, Jackson | |
dc.contributor.author | Sakuishi, Kaori | |
dc.contributor.author | Kurtulus, Sema | |
dc.contributor.author | Gennert, David | |
dc.contributor.author | Xia, Junrong | |
dc.contributor.author | Kwon, John Y.H. | |
dc.contributor.author | Nevin, James | |
dc.contributor.author | Herbst, Rebecca H. | |
dc.contributor.author | Yanai, Itai | |
dc.contributor.author | Rozenblatt-Rosen, Orit | |
dc.contributor.author | Kuchroo, Vijay K. | |
dc.contributor.author | Anderson, Ana C. | |
dc.contributor.author | Marjanovic, Nemanja | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Wang, Chao | |
dc.date.accessioned | 2018-07-03T17:25:17Z | |
dc.date.available | 2018-07-03T17:25:17Z | |
dc.date.issued | 2016-09 | |
dc.date.submitted | 2016-08 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.issn | 1097-4172 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116761 | |
dc.description.abstract | Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8+tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8+TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact. | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/J.CELL.2016.08.052 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.title | A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Singer, Meromit et al. “A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.” Cell 166, 6 (September 2016): 1500–1511 © 2016 Elsevier Inc | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Computational and Systems Biology Program | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Marjanovic, Nemanja | |
dc.contributor.mitauthor | Regev, Aviv | |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-07-03T13:26:38Z | |
dspace.orderedauthors | Singer, Meromit; Wang, Chao; Cong, Le; Marjanovic, Nemanja D.; Kowalczyk, Monika S.; Zhang, Huiyuan; Nyman, Jackson; Sakuishi, Kaori; Kurtulus, Sema; Gennert, David; Xia, Junrong; Kwon, John Y.H.; Nevin, James; Herbst, Rebecca H.; Yanai, Itai; Rozenblatt-Rosen, Orit; Kuchroo, Vijay K.; Regev, Aviv; Anderson, Ana C. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
mit.license | PUBLISHER_CC | en_US |