キラーT細胞のエネルギー代謝機構の解析とPD-1阻害がん免疫治療の効果予測
キラーT細胞のエネルギー代謝機構の解析とPD-1阻害がん免疫治療の効果予測
批准号:
18J15051
负责人:
Kumar Alok
金额:
$1.22万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for JSPS Fellows
财政年份:
2018
资助国家:
日本
项目状态:
已结题
起止时间:
2018-04-25 至 2020-03-31
中文摘要
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英文摘要
We classified unresponsiveness reasons into i). unresponsvieness because of local reasons ii). unresponsiveness because of having systemic immunosuppressive property (SIP). In addition, we found immune response after PD-1 blockade is associated with mitochondrial activation. Based on this result, we concluded that mitochondrial activation could be biomarker to identify responder and nonresponders. Further, we found SIP-positive tumors release non-proteinaceous small molecule that inhibit mitochondrial activation and proliferation of T cells. Bezafibrate when used alongwith culture superntant cancels the suppressive effect of supernatnat. Bezafibrate treatment alongwith PD-1 blockade enhances the survival of host bearing SIP-positive tumor compared to PD-1 blockade alone.
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DOI:
10.7554/elife.52330
发表时间:
2020-03-03
期刊:
ELIFE
影响因子:
7.7
作者:
[Kumar, Alok, Chamoto, Kenji, Honjo, Tasuku]
通讯作者:
Honjo, Tasuku
DOI:
--
发表时间:
2018
期刊:
影响因子:
--
作者:
[Kumar, A.]
通讯作者:
A.
Inhibition of mitochondria by tumor-derived small molecule leads to systemic unresponsiveness to PD-1 blockade therapy
肿瘤源性小分子对线粒体的抑制导致全身对 PD-1 阻断疗法无反应
DOI:
--
发表时间:
2019
期刊:
影响因子:
--
作者:
[Alok Kumar, Kenji Chamoto, Tasuku Honjo]
通讯作者:
Tasuku Honjo
Bezafibrate enhances PD-1 blockade efficacy by activating mitochondrial biogenesis and effector function of CTLs
Bezafibrate 通过激活线粒体生物合成和 CTL 效应器功能来增强 PD-1 阻断功效
DOI:
--
发表时间:
2018
期刊:
影响因子:
--
作者:
[Kumar, A.]
通讯作者:
A.
海外基金