{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:00:34Z","timestamp":1779296434143,"version":"3.51.4"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"7549","license":[{"start":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T00:00:00Z","timestamp":1429660800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T00:00:00Z","timestamp":1429660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2015,4,30]]},"DOI":"10.1038\/nature14426","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T06:35:13Z","timestamp":1429684513000},"page":"692-696","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1140,"title":["Mutant MHC class II epitopes drive therapeutic immune responses to cancer"],"prefix":"10.1038","volume":"520","author":[{"given":"Sebastian","family":"Kreiter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Vormehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"van de Roemer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Diken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"L\u00f6wer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Diekmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Boegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Schr\u00f6rs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvia","family":"Vascotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Castle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arbel D.","family":"Tadmor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Schoenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zlem","family":"T\u00fcreci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugur","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,4,22]]},"reference":[{"key":"BFnature14426_CR1","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1158\/0008-5472.CAN-11-3722","volume":"72","author":"JC Castle","year":"2012","unstructured":"Castle, J. C. et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 72, 1081\u20131091 (2012).","journal-title":"Cancer Res."},{"key":"BFnature14426_CR2","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/1471-2164-15-190","volume":"15","author":"JC Castle","year":"2014","unstructured":"Castle, J. C. et al. Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma. BMC Genomics 15, 190 (2014).","journal-title":"BMC Genomics"},{"key":"BFnature14426_CR3","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1182\/blood-2006-04-015024","volume":"108","author":"S Holtkamp","year":"2006","unstructured":"Holtkamp, S. et al. Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. Blood 108, 4009\u20134017 (2006).","journal-title":"Blood"},{"key":"BFnature14426_CR4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.4049\/jimmunol.180.1.309","volume":"180","author":"S Kreiter","year":"2008","unstructured":"Kreiter, S. et al. Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals. J. Immunol. 180, 309\u2013318 (2008).","journal-title":"J. Immunol."},{"key":"BFnature14426_CR5","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/gt.2010.52","volume":"17","author":"AN Kuhn","year":"2010","unstructured":"Kuhn, A. N. et al. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther. 17, 961\u2013971 (2010).","journal-title":"Gene Ther."},{"key":"BFnature14426_CR6","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1084\/jem.185.3.453","volume":"185","author":"MB Bloom","year":"1997","unstructured":"Bloom, M. B. et al. Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. J. Exp. Med. 185, 453\u2013459 (1997).","journal-title":"J. Exp. Med."},{"key":"BFnature14426_CR7","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nature13387","volume":"512","author":"T Schumacher","year":"2014","unstructured":"Schumacher, T. et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 512, 324\u2013327 (2014).","journal-title":"Nature"},{"key":"BFnature14426_CR8","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1126\/science.1251102","volume":"344","author":"E Tran","year":"2014","unstructured":"Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344, 641\u2013645 (2014).","journal-title":"Science"},{"key":"BFnature14426_CR9","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nbt.2708","volume":"31","author":"CM Britten","year":"2013","unstructured":"Britten, C. M. et al. The regulatory landscape for actively personalized cancer immunotherapies. Nature Biotechnol. 31, 880\u2013882 (2013).","journal-title":"Nature Biotechnol."},{"key":"BFnature14426_CR10","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJMoa1113205","volume":"366","author":"M Gerlinger","year":"2012","unstructured":"Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883\u2013892 (2012).","journal-title":"N. Engl. J. Med."},{"key":"BFnature14426_CR11","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/nature06309","volume":"450","author":"CM Koebel","year":"2007","unstructured":"Koebel, C. M. et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450, 903\u2013907 (2007).","journal-title":"Nature"},{"key":"BFnature14426_CR12","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nature10755","volume":"482","author":"H Matsushita","year":"2012","unstructured":"Matsushita, H. et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482, 400\u2013404 (2012).","journal-title":"Nature"},{"key":"BFnature14426_CR13","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nm.3161","volume":"19","author":"PF Robbins","year":"2013","unstructured":"Robbins, P. F. et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nature Med. 19, 747\u2013752 (2013).","journal-title":"Nature Med."},{"key":"BFnature14426_CR14","doi-asserted-by":"publisher","first-page":"e439","DOI":"10.1200\/JCO.2012.47.7521","volume":"31","author":"N van Rooij","year":"2013","unstructured":"van Rooij, N. et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol. 31, e439\u2013e442 (2013).","journal-title":"J. Clin. Oncol."},{"key":"BFnature14426_CR15","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.4049\/jimmunol.158.6.2723","volume":"158","author":"Z Shen","year":"1997","unstructured":"Shen, Z. et al. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723\u20132720 (1997).","journal-title":"J. Immunol."},{"key":"BFnature14426_CR16","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/31002","volume":"393","author":"SP Schoenberger","year":"1998","unstructured":"Schoenberger, S. P. et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40\u2013CD40L interactions. Nature 393, 480\u2013483 (1998).","journal-title":"Nature"},{"key":"BFnature14426_CR17","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nm.3773","volume":"21","author":"C Linnemann","year":"2015","unstructured":"Linnemann, C. et al. High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nature Med. 21, 81\u201385 (2015).","journal-title":"Nature Med."},{"key":"BFnature14426_CR18","doi-asserted-by":"publisher","first-page":"739","DOI":"10.4049\/jimmunol.169.2.739","volume":"169","author":"PY Arnold","year":"2002","unstructured":"Arnold, P. Y. et al. The majority of immunogenic epitopes generate CD4+ T cells that are dependent on MHC class II-bound peptide-flanking residues. J. Immunol. 169, 739\u2013749 (2002).","journal-title":"J. Immunol."},{"key":"BFnature14426_CR19","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1126\/science.7652577","volume":"269","author":"T Wolfel","year":"1995","unstructured":"Wolfel, T. et al. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269, 1281\u20131284 (1995).","journal-title":"Science"},{"key":"BFnature14426_CR20","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1126\/science.284.5418.1351","volume":"284","author":"RF Wang","year":"1999","unstructured":"Wang, R. F. et al. Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen. Science 284, 1351\u20131354 (1999).","journal-title":"Science"},{"key":"BFnature14426_CR21","doi-asserted-by":"publisher","first-page":"6034","DOI":"10.4049\/jimmunol.1202830","volume":"190","author":"YC Lu","year":"2013","unstructured":"Lu, Y. C. et al. Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression. J. Immunol. 190, 6034\u20136042 (2013).","journal-title":"J. Immunol."},{"key":"BFnature14426_CR22","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nature13988","volume":"515","author":"MM Gubin","year":"2014","unstructured":"Gubin, M. M. et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515, 577\u2013581 (2014).","journal-title":"Nature"},{"key":"BFnature14426_CR23","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","volume":"371","author":"A Snyder","year":"2014","unstructured":"Snyder, A. et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2189\u20132199 (2014).","journal-title":"N. Engl. J. Med."},{"key":"BFnature14426_CR24","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nature14011","volume":"515","author":"RS Herbst","year":"2014","unstructured":"Herbst, R. S. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563\u2013567 (2014).","journal-title":"Nature"},{"key":"BFnature14426_CR25","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/nature13954","volume":"515","author":"PC Tumeh","year":"2014","unstructured":"Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568\u2013571 (2014).","journal-title":"Nature"},{"key":"BFnature14426_CR26","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1126\/science.aaa1348","volume":"348","author":"NA Rizvi","year":"2015","unstructured":"Rizvi, N. A. et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124\u2013128 (2015).","journal-title":"Science"},{"key":"BFnature14426_CR27","doi-asserted-by":"publisher","first-page":"4743","DOI":"10.1038\/srep04743","volume":"4","author":"JC Castle","year":"2014","unstructured":"Castle, J. C. et al. Mutated tumor alleles are expressed according to their DNA frequency. Sci. Rep. 4, 4743 (2014).","journal-title":"Sci. Rep."},{"key":"BFnature14426_CR28","doi-asserted-by":"publisher","first-page":"e1002714","DOI":"10.1371\/journal.pcbi.1002714","volume":"8","author":"M L\u00f6wer","year":"2012","unstructured":"L\u00f6wer, M. et al. Confidence-based somatic mutation evaluation and prioritization. PLOS Comput. Biol. 8, e1002714 (2012).","journal-title":"PLOS Comput. Biol."},{"key":"BFnature14426_CR29","doi-asserted-by":"publisher","first-page":"e954893","DOI":"10.4161\/21624011.2014.954893","volume":"3","author":"S Boegel","year":"2014","unstructured":"Boegel, S. et al. A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines. OncoImmunology 3, e954893 (2014).","journal-title":"OncoImmunology"},{"key":"BFnature14426_CR30","doi-asserted-by":"publisher","first-page":"9031","DOI":"10.1158\/0008-5472.CAN-10-0699","volume":"70","author":"S Kreiter","year":"2010","unstructured":"Kreiter, S. et al. Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res. 70, 9031\u20139040 (2010).","journal-title":"Cancer Res."}],"updated-by":[{"DOI":"10.1038\/nature14567","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000}}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature14426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature14426","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature14426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T14:00:55Z","timestamp":1691589655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature14426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,22]]},"references-count":30,"journal-issue":{"issue":"7549","published-print":{"date-parts":[[2015,4,30]]}},"alternative-id":["BFnature14426"],"URL":"https:\/\/doi.org\/10.1038\/nature14426","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725444872.793506737","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.725444872.793521179","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,22]]},"assertion":[{"value":"7 November 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}