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dc.contributor.authorBurger, Megan L
dc.contributor.authorCruz, Amanda M
dc.contributor.authorCrossland, Grace E
dc.contributor.authorGaglia, Giorgio
dc.contributor.authorRitch, Cecily C
dc.contributor.authorBlatt, Sarah E
dc.contributor.authorBhutkar, Arjun
dc.contributor.authorCanner, David
dc.contributor.authorKienka, Tamina
dc.contributor.authorTavana, Sara Z
dc.contributor.authorBarandiaran, Alexia L
dc.contributor.authorGarmilla, Andrea
dc.contributor.authorSchenkel, Jason M
dc.contributor.authorHillman, Michelle
dc.contributor.authorde los Rios Kobara, Izumi
dc.contributor.authorLi, Amy
dc.contributor.authorJaeger, Alex M
dc.contributor.authorHwang, William L
dc.contributor.authorWestcott, Peter MK
dc.contributor.authorManos, Michael P
dc.contributor.authorHolovatska, Marta M
dc.contributor.authorHodi, F Stephen
dc.contributor.authorRegev, Aviv
dc.contributor.authorSantagata, Sandro
dc.contributor.authorJacks, Tyler
dc.date.accessioned2022-12-09T18:25:19Z
dc.date.available2022-12-09T18:25:19Z
dc.date.issued2021
dc.identifier.urihttps://hdl.handle.net/1721.1/146816
dc.description.abstractCD8 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.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/J.CELL.2021.08.020en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleAntigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumorsen_US
dc.typeArticleen_US
dc.identifier.citationBurger, 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.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalCellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-12-09T18:06:44Z
dspace.orderedauthorsBurger, 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, Ten_US
dspace.date.submission2022-12-09T18:06:48Z
mit.journal.volume184en_US
mit.journal.issue19en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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