dc.contributor.author | Burger, Megan L | |
dc.contributor.author | Cruz, Amanda M | |
dc.contributor.author | Crossland, Grace E | |
dc.contributor.author | Gaglia, Giorgio | |
dc.contributor.author | Ritch, Cecily C | |
dc.contributor.author | Blatt, Sarah E | |
dc.contributor.author | Bhutkar, Arjun | |
dc.contributor.author | Canner, David | |
dc.contributor.author | Kienka, Tamina | |
dc.contributor.author | Tavana, Sara Z | |
dc.contributor.author | Barandiaran, Alexia L | |
dc.contributor.author | Garmilla, Andrea | |
dc.contributor.author | Schenkel, Jason M | |
dc.contributor.author | Hillman, Michelle | |
dc.contributor.author | de los Rios Kobara, Izumi | |
dc.contributor.author | Li, Amy | |
dc.contributor.author | Jaeger, Alex M | |
dc.contributor.author | Hwang, William L | |
dc.contributor.author | Westcott, Peter MK | |
dc.contributor.author | Manos, Michael P | |
dc.contributor.author | Holovatska, Marta M | |
dc.contributor.author | Hodi, F Stephen | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Santagata, Sandro | |
dc.contributor.author | Jacks, Tyler | |
dc.date.accessioned | 2022-12-09T18:25:19Z | |
dc.date.available | 2022-12-09T18:25:19Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/146816 | |
dc.description.abstract | CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdominant antigens were enriched for a TCF1+ progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1+ cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencing datasets revealed that CCR6+ TCF1+ cells exist across human cancers and are not correlated with ICB response. Vaccination eliminated CCR6+ TCF1+ cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors. | en_US |
dc.language.iso | en | |
dc.publisher | Elsevier BV | en_US |
dc.relation.isversionof | 10.1016/J.CELL.2021.08.020 | 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.source | PMC | en_US |
dc.title | Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Burger, Megan L, Cruz, Amanda M, Crossland, Grace E, Gaglia, Giorgio, Ritch, Cecily C et al. 2021. "Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors." Cell, 184 (19). | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
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 | 2022-12-09T18:06:44Z | |
dspace.orderedauthors | Burger, ML; Cruz, AM; Crossland, GE; Gaglia, G; Ritch, CC; Blatt, SE; Bhutkar, A; Canner, D; Kienka, T; Tavana, SZ; Barandiaran, AL; Garmilla, A; Schenkel, JM; Hillman, M; de los Rios Kobara, I; Li, A; Jaeger, AM; Hwang, WL; Westcott, PMK; Manos, MP; Holovatska, MM; Hodi, FS; Regev, A; Santagata, S; Jacks, T | en_US |
dspace.date.submission | 2022-12-09T18:06:48Z | |
mit.journal.volume | 184 | en_US |
mit.journal.issue | 19 | en_US |
mit.license | PUBLISHER_CC | |
mit.metadata.status | Authority Work and Publication Information Needed | en_US |