IFN gamma-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

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dc.contributor.authorNirschl, Christopher J.ko
dc.contributor.authorSuarez-Farinas, Mayteko
dc.contributor.authorIzar, Benjaminko
dc.contributor.authorPrakadan, Sanjayko
dc.contributor.authorDannenfelser, Ruthko
dc.contributor.authorTirosh, Itayko
dc.contributor.authorLiu, Yongko
dc.contributor.authorZhu, Qianko
dc.contributor.authorDevi, K. Sanjana P.ko
dc.contributor.authorCarroll, Shaina L.ko
dc.contributor.authorChau, Davidko
dc.contributor.authorRezaee, Melikako
dc.contributor.authorKim, Tae-Gyunko
dc.contributor.authorHuang, Ruiqiko
dc.contributor.authorFuentes-Duculan, Judilynko
dc.contributor.authorSong-Zhao, George X.ko
dc.contributor.authorGulati, Nicholasko
dc.contributor.authorLowes, Michelle A.ko
dc.contributor.authorKing, Sandra L.ko
dc.contributor.authorQuintana, Francisco J.ko
dc.contributor.authorLee, Young-sukko
dc.contributor.authorKrueger, James G.ko
dc.contributor.authorSarin, Kavita Y.ko
dc.contributor.authorYoon, Charles H.ko
dc.contributor.authorGarraway, Leviko
dc.contributor.authorRegev, Avivko
dc.contributor.authorShalek, Alex K.ko
dc.contributor.authorTroyanskaya, Olgako
dc.contributor.authorAnandasabapathy, Niroshanako
dc.date.accessioned2021-02-01T01:10:26Z-
dc.date.available2021-02-01T01:10:26Z-
dc.date.created2021-02-01-
dc.date.issued2017-06-
dc.identifier.citationCELL, v.170, no.1, pp.127 - +-
dc.identifier.issn0092-8674-
dc.identifier.urihttp://hdl.handle.net/10203/280419-
dc.description.abstractHomeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFN gamma is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFN gamma-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFN gamma. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.-
dc.languageEnglish-
dc.publisherCELL PRESS-
dc.titleIFN gamma-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment-
dc.typeArticle-
dc.identifier.wosid000404358500015-
dc.identifier.scopusid2-s2.0-85021662906-
dc.type.rimsART-
dc.citation.volume170-
dc.citation.issue1-
dc.citation.beginningpage127-
dc.citation.endingpage+-
dc.citation.publicationnameCELL-
dc.identifier.doi10.1016/j.cell.2017.06.016-
dc.contributor.localauthorLee, Young-suk-
dc.contributor.nonIdAuthorNirschl, Christopher J.-
dc.contributor.nonIdAuthorSuarez-Farinas, Mayte-
dc.contributor.nonIdAuthorIzar, Benjamin-
dc.contributor.nonIdAuthorPrakadan, Sanjay-
dc.contributor.nonIdAuthorDannenfelser, Ruth-
dc.contributor.nonIdAuthorTirosh, Itay-
dc.contributor.nonIdAuthorLiu, Yong-
dc.contributor.nonIdAuthorZhu, Qian-
dc.contributor.nonIdAuthorDevi, K. Sanjana P.-
dc.contributor.nonIdAuthorCarroll, Shaina L.-
dc.contributor.nonIdAuthorChau, David-
dc.contributor.nonIdAuthorRezaee, Melika-
dc.contributor.nonIdAuthorKim, Tae-Gyun-
dc.contributor.nonIdAuthorHuang, Ruiqi-
dc.contributor.nonIdAuthorFuentes-Duculan, Judilyn-
dc.contributor.nonIdAuthorSong-Zhao, George X.-
dc.contributor.nonIdAuthorGulati, Nicholas-
dc.contributor.nonIdAuthorLowes, Michelle A.-
dc.contributor.nonIdAuthorKing, Sandra L.-
dc.contributor.nonIdAuthorQuintana, Francisco J.-
dc.contributor.nonIdAuthorKrueger, James G.-
dc.contributor.nonIdAuthorSarin, Kavita Y.-
dc.contributor.nonIdAuthorYoon, Charles H.-
dc.contributor.nonIdAuthorGarraway, Levi-
dc.contributor.nonIdAuthorRegev, Aviv-
dc.contributor.nonIdAuthorShalek, Alex K.-
dc.contributor.nonIdAuthorTroyanskaya, Olga-
dc.contributor.nonIdAuthorAnandasabapathy, Niroshana-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusMIGRATORY DENDRITIC CELLS-
dc.subject.keywordPlusINTERFERON-GAMMA-
dc.subject.keywordPlusFUNCTIONAL SPECIALIZATION-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordPlusRESIDENT-
dc.subject.keywordPlusCANCER-
dc.subject.keywordPlusAUTOIMMUNITY-
dc.subject.keywordPlusMACROPHAGES-
dc.subject.keywordPlusEXPLORATION-
dc.subject.keywordPlusMECHANISMS-
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