{"created":"2024-10-29T00:32:47.079828+00:00","id":2006455,"links":{},"metadata":{"_buckets":{"deposit":"1e3e2344-4830-46f1-9382-88c509d47bed"},"_deposit":{"created_by":7,"id":"2006455","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2006455"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02006455","sets":["1713853213384:1713853296295:1716267876683:1716268551628"]},"author_link":["580","919","528","384","950","1634","450","876","723"],"control_number":"2006455","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"インターフェロン-γと協調したパノビノスタットによる骨髄腫細胞のPD-L1発現誘導","subitem_alternative_title_language":"ja"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019-03-08","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"20","bibliographicPageEnd":"1917","bibliographicPageStart":"1903","bibliographicVolumeNumber":"10","bibliographic_titles":[{"bibliographic_title":"Oncotarget","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Immunotherapy is revolutionizing the treatment paradigm for multiple myeloma (MM). Interferon (IFN)-γ is essential for immune responses, whereas immune checkpoint molecules, such as programmed cell death-1 ligand-1 (PD-L1), mitigate the beneficial anti-tumor immune responses. As HDAC inhibitors alter the immunogenicity and anti-tumor immune responses, we here explored the regulation of PD-L1 expression in MM cells by the clinically available HDAC inhibitor panobinostat in the presence of IFN-γ. IFN-γ activated the STAT1-IRF1 pathway to upregulate PD-L1 expression in MM cells, and panobinostat was able to upregulate their PD-L1 expression without activating the STAT1-IRF1 pathway. Of note, panobinostat enhanced IFN-γR1 expression, which substantially increased the total and phosphorylated levels of STAT1 protein but reduced IRF1 protein levels through proteasomal degradation in the presence of IFN-γ. Panobinostat further enhanced the IFN-γ-mediated durable STAT1 activation in MM cells; STAT1 gene silencing abolished the PD-L1 upregulation by panobinostat and IFN-γ in combination, indicating a critical role for STAT1. These results suggest that panobinostat enhances PD-L1 expression by facilitating the IFN-γ-STAT1 pathway in a ligand-dependent manner in MM cells with ambient IFN-γ. PD-L1 upregulation should be taken into account when combining immunotherapies with panobinostat.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Impact Journals, LLC","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"Copyright: Iwasa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"19492553","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3268号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-22"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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myeloma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"panobinostat","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"PD-L1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"STAT1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"IFN-γR1","subitem_subject_language":"en","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":"PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"PD-L1 upregulation in myeloma cells by panobinostat in combination with 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