PD‑1 blockade therapy augments the antitumor effects of lymphodepletion and adoptive T cell transfer

Persistent ID (NDL): info:ndljp/pid/12769046

Material type: 博士論文

Author: Takahashi, Miho

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Publication date: 2022-03-23

Material Format: Digital

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Name of awarding university/degree: 新潟大学,博士（医学）

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Note (General)：: Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of anti...

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Material Type: 博士論文
Title: PD‑1 blockade therapy augments the antitumor effects of lymphodepletion and adoptive T cell transfer
Author/Editor: Takahashi, Miho
Author Heading: Takahashi, Miho
Publication Date: 2022-03-23
Publication Date (W3CDTF): 2022-03-23
Alternative Title: 抗PD-1抗体治療はリンパ球除去とT細胞移入という養子免疫療法による抗腫瘍効果を高増強する
Degree grantor/type: 新潟大学
Date Granted: 2022-03-23
Date Granted (W3CDTF): 2022-03-23
Dissertation Number: 甲第4981号
Degree Type: 博士（医学）
Text Language Code: eng
Alias of Author: 髙橋, 美帆
Subject Heading: Lymphodepletion
PD-1
T cell
Immune checkpoint
Target Audience: 一般
Note (General): Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.
Cancer Immunology, Immunotherapy. 2022, 71(6), 1357-1369.
新大院博(医)第1051号
Persistent ID (NDL): info:ndljp/pid/12769046
https://dl.ndl.go.jp/pid/12769046
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
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Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2023-04-07T23:08:38+09:00
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
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Availability of remote photoduplication service: 可
Periodical Title (URI): http://hdl.handle.net/10191/0002000837
https://niigata-u.repo.nii.ac.jp/records/2000837
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
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