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Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer\/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion\/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.<\/jats:p>","DOI":"10.3390\/ijms25073660","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:47:11Z","timestamp":1711370831000},"page":"3660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Birinapant Reshapes the Tumor Immunopeptidome and Enhances Antigen Presentation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3888-0296","authenticated-orcid":false,"given":"Weiyan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Bakar Computational Health Sciences Institute, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delan","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengju","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-8271","authenticated-orcid":false,"given":"Qingsong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Ji","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/10408360902937809","article-title":"Cancer immunotherapy","volume":"46","author":"Baxevanis","year":"2009","journal-title":"Crit. 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