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dc.contributor.authorDuPage, Michel J.
dc.contributor.authorMazumdar, Claire
dc.contributor.authorSchmidt, Leah Marie
dc.contributor.authorCheung, Ann
dc.contributor.authorJacks, Tyler E.
dc.date.accessioned2012-09-28T17:28:47Z
dc.date.available2012-09-28T17:28:47Z
dc.date.issued2012-02
dc.date.submitted2011-08
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.urihttp://hdl.handle.net/1721.1/73483
dc.description.abstractCancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1, 2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced2, 3. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant 1 U54 CA126515-01)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)en_US
dc.description.sponsorshipMargaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Awarden_US
dc.description.sponsorshipJohnD. Proctor Foundationen_US
dc.description.sponsorshipDaniel K. Ludwig Scholaren_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nature10803en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.rights.urien_US
dc.sourcePMCen_US
dc.titleExpression of tumour-specific antigens underlies cancer immunoeditingen_US
dc.typeArticleen_US
dc.identifier.citationDuPage, Michel J. et al. “Expression of Tumour-specific Antigens Underlies Cancer Immunoediting.” Nature 482.7385 (2012): 405–409.en_US
dc.contributor.departmentmove to dc.description.sponsorshipen_US
dc.contributor.departmentmove to dc.description.sponsorshipen_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. School of Scienceen_US
dc.contributor.mitauthorDuPage, Michel J.
dc.contributor.mitauthorMazumdar, Claire
dc.contributor.mitauthorSchmidt, Leah Marie
dc.contributor.mitauthorCheung, Ann
dc.contributor.mitauthorJacks, Tyler E.
dc.relation.journalNatureen_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
dspace.orderedauthorsDuPage, Michel; Mazumdar, Claire; Schmidt, Leah M.; Cheung, Ann F.; Jacks, Tyleren
dc.identifier.orcidhttps://orcid.org/0000-0001-5785-8911
dc.identifier.orcidhttps://orcid.org/0000-0001-9076-8475
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US


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