{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:43:28Z","timestamp":1773931408251,"version":"3.50.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"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\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070672"],"award-info":[{"award-number":["32070672"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170674"],"award-info":[{"award-number":["32170674"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intertumoral immune heterogeneity is a critical reason for distinct clinical benefits of immunotherapy in lung adenocarcinoma (LUAD). Tumor immunophenotype (immune \u2018Hot\u2019 or \u2018Cold\u2019) suggests immunological individual differences and potential clinical treatment guidelines. However, employing epigenome signatures to determine tumor immunophenotypes and responsive treatment is not well understood. To delineate the tumor immunophenotype and immune heterogeneity, we first distinguished the immune \u2018Hot\u2019 and \u2018Cold\u2019 tumors of LUAD based on five immune expression signatures. In terms of clinical presentation, the immune \u2018Hot\u2019 tumors usually had higher immunoactivity, lower disease stages and better survival outcomes than \u2018Cold\u2019 tumors. At the epigenome levels, we observed that distinct DNA methylation patterns between immunophenotypes were closely associated with LUAD development. Hence, we identified a set of five CpG sites as the immunophenotype-related methylation signature (iPMS) for tumor immunophenotyping and further confirmed its efficiency based on a machine learning framework. Furthermore, we found iPMS and immunophenotype-related immune checkpoints (IPCPs) could contribute to the risk of tumor progression, implying IPCP has the potential to be a novel immunotherapy blockade target. After further parsing of the role of iPMS-predicted immunophenotypes, we found immune \u2018Hot\u2019 was a protective factor leading to better survival outcomes when patients received the anti-PD-1\/PD-L1 immunotherapy. And iPMS was also a well-performed signature (AUC\u2009=\u20090.752) for predicting the durable\/nondurable clinical benefits. In summary, our study explored the role of epigenome signature in clinical tumor immunophenotyping. Utilizing iPMS to characterize tumor immunophenotypes will facilitate developing personalized epigenetic anticancer approaches.<\/jats:p>","DOI":"10.1093\/bib\/bbab481","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T16:49:21Z","timestamp":1634748561000},"source":"Crossref","is-referenced-by-count":19,"title":["Epigenome signature as an immunophenotype indicator prompts durable clinical immunotherapy benefits in lung adenocarcinoma"],"prefix":"10.1093","volume":"23","author":[{"given":"Xu","family":"Pan","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}]},{"given":"Caiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}]},{"given":"Junwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The 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Science and Technology, Harbin Medical University, Harbin 150081, China"},{"name":"Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9103-8642","authenticated-orcid":false,"given":"Hui","family":"Zhi","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-8945","authenticated-orcid":false,"given":"Shangwei","family":"Ning","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}]}],"member":"286","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"2022012000303296600_ref1","first-page":"514","article-title":"Cancer immunotherapy, part 3: challenges and future trends","volume":"42","author":"Ventola","year":"2017","journal-title":"P & T: a peer-reviewed 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