{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:19:01Z","timestamp":1779178741899,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17H06162"],"award-info":[{"award-number":["17H06162"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["16K15551"],"award-info":[{"award-number":["16K15551"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19K16827"],"award-info":[{"award-number":["19K16827"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Projects for Cancer Research by Therapeutic Evolution"},{"name":"Development of Technology for Patient Stratification Biomarker Discovery","award":["19ae0101074s0401"],"award-info":[{"award-number":["19ae0101074s0401"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Center Research and Development Fund","award":["28-A-7"],"award-info":[{"award-number":["28-A-7"]}]},{"name":"National Cancer Center Research and Development Fund","award":["31-A-7"],"award-info":[{"award-number":["31-A-7"]}]},{"name":"Shinshu University Hospital and Shinshu Igaku Shinkokai"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumor neoantigens derived from genetic alterations are potential T-cell targets for antitumor immunity. However, tumors develop immune escape mechanisms including loss of preexisting neoantigens and\/or impairment of T-cell responses during tumor development and progression. Here, we addressed whether newly emerged immunogenic neoantigens in established tumors enabled hosts to inhibit tumor growth via controlling immune escape mechanisms. Using a doxycycline-driven gene expression system, we generated murine MC38, CT26 (colorectal cancer) and B16 (melanoma) cell lines with inducible expression of model immunogenic neoantigens such as chicken ovalbumin and human NY-ESO-1. A model neoantigen was induced by doxycycline administration in the tumors once tumors became palpable. Tumor growth was significantly inhibited upon induction of the neoantigen and this inhibition was abrogated in nude mice lacking T cells and in mice deprived of CD8+ T cells, indicating the critical role of CD8+ T cells in tumor regression. In addition, PD-1\/PD-L1 blockade further augmented the antitumor immune response, resulting in a far stronger inhibition of tumor growth. Accordingly, newly emerged tumor neoantigen-specific CD8+ T cells with enhanced effector functions were significantly increased in mice treated with PD-1\/PD-L1 blockade. We propose that a newly emerged neoantigen is sufficient to inhibit tumor growth via preventing immune escape in a T-cell-dependent manner. Our results imply that induction of immunogenic tumor neoantigens is a novel strategy to overcome the resistance to immune checkpoint blockade therapy.<\/jats:p>","DOI":"10.1093\/intimm\/dxaa049","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T18:04:55Z","timestamp":1596132295000},"page":"39-48","source":"Crossref","is-referenced-by-count":5,"title":["Newly emerged immunogenic neoantigens in established tumors enable hosts to regain immunosurveillance in a T-cell-dependent manner"],"prefix":"10.1093","volume":"33","author":[{"given":"Tomoaki","family":"Muramatsu","sequence":"first","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"},{"name":"Department of Urology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuro","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hokkaido University Graduate School of Medicine , Sapporo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshie","family":"Kanada","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"},{"name":"Department of Urology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Fujimaki","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momokazu","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Urology, Nagoya University Graduate School of Medicine , Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyoshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine , Nagoya, Japan"},{"name":"Division of Cancer Immunology, Research Institute, National Cancer Center , Tokyo, Japan"},{"name":"Division of Cancer Immunology, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center , Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"2022070716063061300_CIT0001","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"Schumacher","year":"2015","journal-title":"Science"},{"key":"2022070716063061300_CIT0002","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1126\/science.1203486","article-title":"Cancer immunoediting: integrating immunity\u2019s roles in cancer suppression and promotion","volume":"331","author":"Schreiber","year":"2011","journal-title":"Science"},{"key":"2022070716063061300_CIT0003","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccell.2015.03.001","article-title":"Immune checkpoint blockade: a common denominator approach to cancer therapy","volume":"27","author":"Topalian","year":"2015","journal-title":"Cancer Cell"},{"key":"2022070716063061300_CIT0004","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. 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Mater"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxaa049\/33676343\/dxaa049.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/33\/1\/39\/44562551\/dxaa049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/33\/1\/39\/44562551\/dxaa049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T16:07:10Z","timestamp":1657210030000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/33\/1\/39\/5878926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,7,30]]},"published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxaa049","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2020,7,30]]}}}