dc.contributor.author | Nirschl, Christopher J. | |
dc.contributor.author | Suárez-Fariñas, Mayte | |
dc.contributor.author | Izar, Benjamin | |
dc.contributor.author | Dannenfelser, Ruth | |
dc.contributor.author | Tirosh, Itay | |
dc.contributor.author | Liu, Yong | |
dc.contributor.author | Zhu, Qian | |
dc.contributor.author | Devi, K. Sanjana P. | |
dc.contributor.author | Chau, David | |
dc.contributor.author | Rezaee, Melika | |
dc.contributor.author | Kim, Tae-Gyun | |
dc.contributor.author | Huang, Ruiqi | |
dc.contributor.author | Fuentes-Duculan, Judilyn | |
dc.contributor.author | Song-Zhao, George X. | |
dc.contributor.author | Gulati, Nicholas | |
dc.contributor.author | Lowes, Michelle A. | |
dc.contributor.author | King, Sandra L. | |
dc.contributor.author | Quintana, Francisco J. | |
dc.contributor.author | Lee, Young-suk | |
dc.contributor.author | Krueger, James G. | |
dc.contributor.author | Sarin, Kavita Y. | |
dc.contributor.author | Yoon, Charles H. | |
dc.contributor.author | Troyanskaya, Olga | |
dc.contributor.author | Anandasabapathy, Niroshana | |
dc.contributor.author | Prakadan, Sanjay | |
dc.contributor.author | Carroll, Shaina Laufer | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Shalek, Alexander K | |
dc.contributor.author | Garraway, Levi A. | |
dc.date.accessioned | 2018-07-02T20:13:51Z | |
dc.date.available | 2018-07-02T20:13:51Z | |
dc.date.issued | 2017-06 | |
dc.date.submitted | 2017-03 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.issn | 1097-4172 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/116738 | |
dc.description.abstract | Homeostatic 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. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-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 IFNγ. 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. Keywords: dendritic cells; homeostasis; differentiation; IFNγ; tumor microenvironment; melanoma tolerance; immunotherapy; suppressor-of-cytokine-signaling 2 (SOCS2); tissue mononuclear phagocytes | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/J.CELL.2017.06.016 | 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 | IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Nirschl, Christopher J. et al. “IFNγ-Dependent Tissue-Immune Homeostasis Is Co-Opted in the Tumor Microenvironment.” Cell 170, 1 (June 2017): 127–141 © 2017 Elsevier Inc | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Prakadan, Sanjay | |
dc.contributor.mitauthor | Carroll, Shaina Laufer | |
dc.contributor.mitauthor | Garraway, Levi | |
dc.contributor.mitauthor | Regev, Aviv | |
dc.contributor.mitauthor | Shalek, Alexander K | |
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 | 2018-07-02T19:20:08Z | |
dspace.orderedauthors | Nirschl, Christopher J.; Suárez-Fariñas, Mayte; Izar, Benjamin; Prakadan, Sanjay; Dannenfelser, Ruth; Tirosh, Itay; Liu, Yong; Zhu, Qian; Devi, K. Sanjana P.; Carroll, Shaina L.; Chau, David; Rezaee, Melika; Kim, Tae-Gyun; Huang, Ruiqi; Fuentes-Duculan, Judilyn; Song-Zhao, George X.; Gulati, Nicholas; Lowes, Michelle A.; King, Sandra L.; Quintana, Francisco J.; Lee, Young-suk; Krueger, James G.; Sarin, Kavita Y.; Yoon, Charles H.; Garraway, Levi; Regev, Aviv; Shalek, Alex K.; Troyanskaya, Olga; Anandasabapathy, Niroshana | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-5621-8768 | |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
dc.identifier.orcid | https://orcid.org/0000-0001-5670-8778 | |
mit.license | PUBLISHER_CC | en_US |