PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ

• Material Type: 博士論文
• ISSN: 1949-2553
• Title: PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ
• Volume: 10 20
• Author/Editor: Iwasa, Masami; Harada, Takeshi; Oda, Asuka; Bat-Erdene, Ariunzaya; Teramachi, Jumpei; Tenshin, Hirofumi; Ashtar, Mohannad; Oura, Masahiro; Sogabe, Kimiko; Udaka, Kengo; Fujii, Shiro; Nakamura, Shingen; Miki, Hirokazu; Kagawa, Kumiko; Ozaki, Shuji; Abe, Masahiro
• Author Heading: Iwasa, Masami; Harada, Takeshi; Oda, Asuka; Bat-Erdene, Ariunzaya; Teramachi, Jumpei; Tenshin, Hirofumi; Ashtar, Mohannad; Oura, Masahiro; Sogabe, Kimiko; Udaka, Kengo; Fujii, Shiro; Nakamura, Shingen; Miki, Hirokazu; Kagawa, Kumiko; Ozaki, Shuji; Abe, Masahiro
• Publication, Distribution, etc.: Impact Journals, LLC
• Publication Date: 2019-03-08
• Publication Date (W3CDTF): 2019-03-08
• 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
• Periodical title: Oncotarget
• Degree grantor/type: 徳島大学
• Date Granted: 2019-03-22
• Date Granted (W3CDTF): 2019-03-22
• Dissertation Number: 甲第3268号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3268号
• Text Language Code: eng
• Subject Heading: Multiple myeloma; panobinostat; PD-L1; STAT1; IFN-γR1
• Target Audience: 一般
• Note (General): 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.
• DOI: info:doi/10.18632/oncotarget.26726; https://doi.org/info:doi/10.18632/oncotarget.26726
• Persistent ID (NDL): info:ndljp/pid/11300545; https://dl.ndl.go.jp/pid/11300545
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-07-05T01:13:02+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/113359
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp