PD-1 efficiently inhibits T cell activation even in the presence of co-stimulation through CD27 and GITR

• Material Type: 博士論文
• ISSN: 0006-291X
• Title: PD-1 efficiently inhibits T cell activation even in the presence of co-stimulation through CD27 and GITR
• Volume: 511 3
• Author/Editor: Mizuno, Reina; Maruhashi, Takumi; Sugiura, Daisuke; Shimizu, Kenji; Watada, Mizuki; Okazaki, Il-mi; Okazaki, Taku
• Author Heading: Mizuno, Reina; Maruhashi, Takumi; Sugiura, Daisuke; Shimizu, Kenji; Watada, Mizuki; Okazaki, Il-mi; Okazaki, Taku
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2019-02-14
• Publication Date (W3CDTF): 2019-02-14
• Alternative Title: PD-1はCD27およびGITRを介した共刺激存在下でもT細胞活性化を効率的に抑制する
• Periodical title: Biochemical and Biophysical Research Communications
• Degree grantor/type: 徳島大学
• Date Granted: 2019-03-19
• Date Granted (W3CDTF): 2019-03-19
• Dissertation Number: 甲第3267号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3267号
• Text Language Code: eng
• Subject Heading: PD-1; CD27; GITR; T cell activation; Co-receptor; TNF receptor super family
• Target Audience: 一般
• Note (General): Cancer immunotherapies targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 revolutionized cancer treatment and instigated various trials to develop new cancer immunotherapies with higher therapeutic efficacy. Agonistic Abs against tumor necrosis factor receptor super family (TNFRSF) molecules are highly expected due to their high potential to enhance survival, proliferation, and effector function of T cells. To date, agonistic antibodies (Abs) against CD27, GITR, OX40, and 4-1BB have been reported to increase the efficacy of anti-PD-1 therapy in animal models and clinical trials of these combinatorial therapies are underway. However, the mechanisms how agonistic Abs against TNFRSF molecules potentiate anti-PD-1 therapy are not well understood. Here we examined the potency of PD-1 to inhibit the antigen-dependent activation of T cells in the presence of co-stimulation through CD27 and GITR by using in vitro and ex vivo co-culture systems of T cells and antigen presenting cells. The cytokine secretion from T cells upon antigen stimulation was strongly augmented by the engagement of CD27 or GITR with their corresponding ligands. Remarkably, PD-1 efficiently inhibited the activation of T cells even in the presence of co-stimulation through CD27 or GITR. Accordingly, cytokine secretion was synergistically augmented when PD-1 blockade was combined with triggering of CD27 or GITR. These results indicate that the triggering of TNFRSF molecules and PD-1 blockade can act on the same individual cells simultaneously to augment the magnitude of T cell activation, providing the rationale for the combinatorial usage of agonistic Abs against TNFRSF molecules and blocking Abs against PD-1 or PD-L1.
• DOI: info:doi/10.1016/j.bbrc.2019.02.004; https://doi.org/info:doi/10.1016/j.bbrc.2019.02.004
• Persistent ID (NDL): info:ndljp/pid/11300295; https://dl.ndl.go.jp/pid/11300295
• 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/113351
• 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