{"created":"2024-12-03T06:13:19.242363+00:00","id":2000710,"links":{},"metadata":{"_buckets":{"deposit":"a2493822-6644-4569-8ad2-855ada9c27e4"},"_deposit":{"created_by":33,"id":"2000710","owner":"33","owners":[33],"pid":{"revision_id":0,"type":"depid","value":"2000710"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:02000710","sets":["7:1707111347047"]},"author_link":[],"control_number":"2000710","item_10006_creator_3":{"attribute_name":"著者(英)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kadyrzhanova, Gulfiya","creatorNameLang":"en"}]}]},"item_10006_date_granted_11":{"attribute_name":"Degree Conferral Date","attribute_value_mlt":[{"subitem_dategranted":"2024-09-30"}]},"item_10006_degree_grantor_9":{"attribute_name":"Degree Conferrral Institution","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"Okinawa Institute of Science and Technology Graduate University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"38005","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"Degree","attribute_value_mlt":[{"subitem_degreename":"Doctor of Philosophy"}]},"item_10006_description_7":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Aging is associated with reduction in diversity of antigen-specificity and activity of T cells. This might be related to an increased prevalence of cancers in people over 65 years old. Accordingly, adoptive T cell therapy (ACT) may be useful to treat cancers in elderly individuals, but the efficacy of ACT in elderly patients remains unclear. In this study, I found that intrinsic aging of CD8+ T cells impairs their anti-tumor activity in a mouse model of ACT with engineered T cells expressing TCR specific to tumor or antigens (TCR-T cells), although it does not affect cytotoxicity of CD8+ TCR-T cells in vitro. Single-cell RNA-sequencing (scRNA-seq) analysis revealed a significant increase in proportion of terminally exhausted cells and a decrease in progenitor exhausted cells in tumor-infiltrating aged TCR-T cells in ACT. Moreover, expression of endothelial PAS domain-containing protein 1 (Epas1) is significantly decreased in aged CD8+ T cells. Crispr-mediated ablation of Epas1 in young CD8+ T cells results in reduction in their anti-tumor activity and accumulation in the tumor in ACT. Moreover, Epas1-deficient tumor-infiltrating cells tend to exhibit the phenotype of terminally exhausted cells. These findings suggest that aging decreases Epas1 expression in CD8+ T cells, which in turn promotes cell exhaustion and decreases their anti-tumor activity. Enhancing Epas1 expression may therefore be a therapeutic strategy to improve the efficacy of ACT in the elderly.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"Degree Referral Number","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第166号"}]},"item_10006_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15102/0002000710","subitem_identifier_reg_type":"JaLC"}]},"item_10006_rights_13":{"attribute_name":"Copyright Information","attribute_value_mlt":[{"subitem_rights":"© 2024 The Author."},{"subitem_rights":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International","subitem_rights_resource":"https://creativecommons.org/licenses/by-nc-nd/4.0/"}]},"item_10006_text_24":{"attribute_name":"Exam Date","attribute_value_mlt":[{"subitem_text_value":"2024-08-15"}]},"item_10006_version_type_18":{"attribute_name":"Version Format","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1731043371613":{"attribute_name":"","attribute_value_mlt":[{"subitem_start_page":"1"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2025-11-03"}],"filename":"KadyrzhanovaGulfiyaFulltext.pdf","filesize":[{"value":"6.1 MB"}],"format":"application/pdf","licensetype":"license_5","mimetype":"application/pdf","url":{"objectType":"other","url":"https://oist.repo.nii.ac.jp/record/2000710/files/KadyrzhanovaGulfiyaFulltext.pdf"},"version_id":"3cfd9b8b-d18d-4783-9062-7ffe9a7f0624"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-03"}],"filename":"KadyrzhanovaGulfiyaExamAbstract.pdf","filesize":[{"value":"48 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"abstract","url":"https://oist.repo.nii.ac.jp/record/2000710/files/KadyrzhanovaGulfiyaExamAbstract.pdf"},"version_id":"e5118c5d-d968-47e5-8c92-b7411afd9013"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-03"}],"filename":"KadyrzhanovaGulfiyaSummary.pdf","filesize":[{"value":"84 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"summary","url":"https://oist.repo.nii.ac.jp/record/2000710/files/KadyrzhanovaGulfiyaSummary.pdf"},"version_id":"dbfdad1b-f59a-4774-bb87-dc1722e568a5"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Anti-tumor cytotoxic CD8 T cell responses | adoptive T cell therapy | aging effects on T cells","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"マウス固形腫瘍に対するT細胞免疫療法における加齢の影響","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"マウス固形腫瘍に対するT細胞免疫療法における加齢の影響","subitem_title_language":"ja"},{"subitem_title":"Aging Effects on Murine Adoptive T cell Therapy for Solid Tumor","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"33","path":["1707111347047"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-12-03"},"publish_date":"2024-12-03","publish_status":"0","recid":"2000710","relation_version_is_last":true,"title":["マウス固形腫瘍に対するT細胞免疫療法における加齢の影響"],"weko_creator_id":"33","weko_shared_id":-1},"updated":"2024-12-04T02:23:37.360534+00:00"}