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However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8+ T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans. These HLA-A*02:01 presented peptides do not derive from the mutanome of cancers, but are of \u201cself\u201d origin and therefore constitute universal neoantigens. Indeed, CD8+ T cells specific for the leader peptide of the ubiquitously expressed LRPAP1 protein recognized TAP-deficient, HLA-Ilow lymphomas, melanomas, and renal and colon carcinomas, but not healthy counterparts. In contrast to personalized mutanome-targeted therapies, these conserved neoantigens and their cognate receptors can be exploited for immune-escaped cancers across diverse histological origins.<\/jats:p>","DOI":"10.1084\/jem.20180577","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T09:34:39Z","timestamp":1534412079000},"page":"2325-2337","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["Identification of non-mutated neoantigens presented by TAP-deficient tumors"],"prefix":"10.1084","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4396-0047","authenticated-orcid":true,"given":"Koen A.","family":"Marijt","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Blijleven","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4449-8707","authenticated-orcid":true,"given":"Els M.E.","family":"Verdegaal","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel G.","family":"Kester","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center, Leiden, Netherlands 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Kowalewski","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, T\u00fcbingen, Germany 3"},{"name":"German Cancer Consortium, German Cancer Research Center, T\u00fcbingen, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2647","authenticated-orcid":true,"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, T\u00fcbingen, Germany 3"},{"name":"German Cancer Consortium, German Cancer Research Center, T\u00fcbingen, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1954-7762","authenticated-orcid":true,"given":"Stefan","family":"Stevanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, T\u00fcbingen, Germany 3"},{"name":"German Cancer Consortium, German Cancer Research Center, T\u00fcbingen, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-9133","authenticated-orcid":true,"given":"Mirjam H.M.","family":"Heemskerk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center, Leiden, Netherlands 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-0354","authenticated-orcid":true,"given":"Sjoerd H.","family":"van der Burg","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9115-558X","authenticated-orcid":true,"given":"Thorbald","family":"van Hall","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"key":"2023072609345367400_bib1","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.4049\/jimmunol.151.7.3407","article-title":"Intracellular transport of class I MHC molecules in antigen processing mutant cell lines","volume":"151","author":"Anderson","year":"1993","journal-title":"J. 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