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

• Material Type: 博士論文
• Title: PD-L1 upregulation in myeloma cells by panobinostat in combination with interferon-γ
• 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
• No. or year of volume/issue: 10 20
• Volume: 10
• Issue: 20
• Pages: 1903-1917
• ISSN (Periodical Title): ISSN : 1949-2553
• Degree grantor/type: 徳島大学
• Date Granted: 2019-03-22
• Dissertation Number: 甲第3268号
• Degree Type: 博士（医学）
• 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): 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.
• Related Material (DOI): 10.18632/oncotarget.26726
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

http://repo.lib.tokushima-u.ac.jp/files/public/11/113359/20190606143149261009/k3268_abstract_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/113359/20190610170724119369/k3268_fulltext.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/113359/20190610170725828688/k3268_supple.pdf fulltext