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dc.contributor.authorPatel, Rupesh S
dc.contributor.authorRomero, Rodrigo
dc.contributor.authorWatson, Emma V
dc.contributor.authorLiang, Anthony C
dc.contributor.authorBurger, Megan
dc.contributor.authorWestcott, Peter MK
dc.contributor.authorMercer, Kim L
dc.contributor.authorBronson, Roderick T
dc.contributor.authorWooten, Eric C
dc.contributor.authorBhutkar, Arjun
dc.contributor.authorJacks, Tyler
dc.contributor.authorElledge, Stephen J
dc.date.accessioned2022-12-09T18:07:18Z
dc.date.available2022-12-09T18:07:18Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/1721.1/146815
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>The GATA4 transcription factor acts as a master regulator of development of multiple tissues. GATA4 also acts in a distinct capacity to control a stress-inducible pro-inflammatory secretory program that is associated with senescence, a potent tumor suppression mechanism, but also operates in non-senescent contexts such as tumorigenesis. This secretory pathway is composed of chemokines, cytokines, growth factors, and proteases. Since GATA4 is deleted or epigenetically silenced in cancer, here we examine the role of GATA4 in tumorigenesis in mouse models through both loss-of-function and overexpression experiments. We find that GATA4 promotes non-cell autonomous tumor suppression in multiple model systems. Mechanistically, we show that <jats:italic>Gata4</jats:italic>-dependent tumor suppression requires cytotoxic CD8 T cells and partially requires the secreted chemokine CCL2. Analysis of transcriptome data in human tumors reveals reduced lymphocyte infiltration in <jats:italic>GATA4</jats:italic>-deficient tumors, consistent with our murine data. Notably, activation of the GATA4-dependent secretory program combined with an anti-PD-1 antibody robustly abrogates tumor growth in vivo.</jats:p>en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1038/S41467-021-27731-5en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceNatureen_US
dc.titleA GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cellsen_US
dc.typeArticleen_US
dc.identifier.citationPatel, Rupesh S, Romero, Rodrigo, Watson, Emma V, Liang, Anthony C, Burger, Megan et al. 2022. "A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells." Nature Communications, 13 (1).
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.relation.journalNature Communicationsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2022-12-09T18:00:26Z
dspace.orderedauthorsPatel, RS; Romero, R; Watson, EV; Liang, AC; Burger, M; Westcott, PMK; Mercer, KL; Bronson, RT; Wooten, EC; Bhutkar, A; Jacks, T; Elledge, SJen_US
dspace.date.submission2022-12-09T18:00:28Z
mit.journal.volume13en_US
mit.journal.issue1en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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