Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb

• Material Type: 博士論文
• ISSN: 0006-291X
• Title: Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb
• Volume: 490 2
• Author/Editor: 上原, 治朗
• Publication Date: 2017-08
• Publication Date (W3CDTF): 2017-08
• Periodical title: Biochemical and biophysical research communications
• Degree grantor/type: 旭川医科大学
• Date Granted: 2018-09-28
• Date Granted (W3CDTF): 2018-09-28
• Dissertation Number: 乙第474号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 乙第474号
• Text Language Code: eng
• Subject Heading: Chemokine; INF-β; Melanoma; Neoantigen; PD-L1
• Note (General): Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues. We therefore investigated whether intratumoral injection of IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma cells and has additional antitumor effects when combined with anti-PD-L1 mAb treatment. IFN-β treatment enhanced CD8+ T-cell infiltration into tumors and CCL5 and CXCR3 ligand expression. In vivo studies using a mouse model showed that monotherapy with IFN-β, but not with anti-PD-L1 mAb, inhibited tumor growth in comparison to control. However, the therapeutic efficacy of IFN-β was significantly enhanced by the addition of anti-PD-L1 mAb. This antitumor response of combination therapy was abrogated by anti-CD8 mAb and IFN-β augmented the neoantigen-specific T-cell response of anti-PD-L1 mAb. Our findings suggest that IFN-β induces the expression of CCL5 and CXCR3 ligands in melanoma, which could play a role in T-cell recruitment, and enhances the efficacy of anti-PD-L1 mAb treatment in a CD8-dependent manner.; identifier:PMID：28624449; 開始ページ : 521; 終了ページ : 527
• DOI: info:doi/10.1016/j.bbrc.2017.06.072; https://doi.org/info:doi/10.1016/j.bbrc.2017.06.072
• Persistent ID (NDL): info:ndljp/pid/11178612; https://dl.ndl.go.jp/pid/11178612
• 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): 2018-11-05T10:48:21+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
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• Periodical Title (URI): http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20180928_O474
• 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