Therapeutic targeting MDSC-mediated immune suppression in cancer
针对癌症中 MDSC 介导的免疫抑制的治疗
基本信息
- 批准号:10540357
- 负责人:
- 金额:$ 68.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-13 至 2026-11-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAlcoholsApoptosisArachidonate 15-LipoxygenaseBiologyBloodBone MarrowCancer PatientCell DeathCell Differentiation processCell physiologyCellsClinicalColon CarcinomaCross PresentationDataDendritic CellsDown-RegulationGenerationsGlutathioneGoalsImmuneImmune responseImmunosuppressionImmunotherapyIronKnowledgeLipid PeroxidationLipid PeroxidesLipidsMacrophageMalignant NeoplasmsMalignant neoplasm of lungMalignant neoplasm of pancreasMediatingMusMyelogenousMyeloid CellsMyeloid-derived suppressor cellsNatural Killer CellsNecrosisNeoplasm MetastasisPathologicPatientsPeroxidasesPhysiologicalPopulationRegulationRoleSamplingSignal TransductionSpleenSystemT cell responseT-LymphocyteTestingTherapeuticTherapeutic EffectTumor EscapeTumor Tissuebone circulationclinically relevantglutathione peroxidasegranulocyteimmunoregulationimprovedlymphoid organmonocytemouse modelneutrophilnovelnovel strategiesoxidationoxidized lipidperipheral lymphoid organphospholipid-hydroperoxide glutathione peroxidasepre-clinicalprogramsrepairedtherapeutic targettreatment effecttumortumor microenvironmenttumor progression
项目摘要
Project Summary
The prominent change in the myeloid compartment in cancer is the expansion of pathologically activated
immature myeloid cells with the potent ability to suppress immune responses – myeloid-derived suppressor cells
(MDSC). In tumor-bearing mice, the total population of MDSC consists of three groups of cells: the most
abundant (>75%) immature, pathologically activated neutrophils (PMN-MDSC); less abundant (<20%)
population of pathologically activated monocytes (M-MDSC); and small (<5%) population of early myeloid
precursors. In the tumor microenvironment MDSC are more immunosuppressive than in peripheral lymphoid
organ. However, the mechanism of this phenomenon remains rather elusive. The gaps in our knowledge is in
understanding the mechanisms regulating the function of MDSC in tumors and specific requirements for their
targeting. In this proposal we will test the hypothesis that there are distinct populations of MDSC in tumors. These
populations can be defined by specific markers and most importantly, have different sensitivity to ferroptotic cell
death which determines their functional activity. We will test the concept that targeting ferroptosis in PMN-MDSC
in cancer may have functional consequences for immune responses. The goal of this project is to uncover the
mechanisms regulating myeloid cell function in tumors and to develop novel approaches to the regulation of
immune responses in cancer.
We propose the following Specific Aims: (1) To identify the mechanism of ferroptosis-mediated immune
suppression induced by PMN-MDSC in tumors; and (2) To investigate therapeutic potential of targeting
ferroptosis in PMN-MDSC.
项目摘要
在癌症中,髓系室的显著变化是病理激活的
具有强大免疫抑制能力的未成熟髓系细胞-髓系来源的抑制细胞
(MDSC)。在荷瘤小鼠中,MDSC的总群体由三组细胞组成:最多的
大量(>;75%)未成熟的、病理激活的中性粒细胞(PMN-MDSC);较少的(<;20%)
病理激活的单核细胞(M-MDSC)群体;以及少量(5%)的早期髓系细胞
先驱物。在肿瘤微环境中,MDSC比外周淋巴组织更具免疫抑制作用
管风琴。然而,这种现象的机制仍然相当难以捉摸。我们知识上的差距在于
了解肿瘤中多药耐药干细胞功能的调节机制及其对其的特殊要求
瞄准目标。在这项建议中,我们将检验假设,即肿瘤中存在不同的MDSC群体。这些
群体可以由特定的标记来定义,最重要的是,对铁链细胞具有不同的敏感性
死亡决定了它们的功能活动。我们将在PMN-MDSC中测试靶向下垂的概念
在癌症中可能对免疫反应产生功能影响。这个项目的目标是揭开
调节肿瘤髓系细胞功能的机制和开发新的调节方法
癌症中的免疫反应。
我们提出了以下具体目标:(1)确定铁下垂介导的免疫机制
PMN-MDSC对肿瘤的抑制作用;(2)研究靶向治疗的可能性
PMN-MDSC的铁性下垂。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Valerian E Kagan其他文献
Role of coenzyme Q and superoxide in vitamin E cycling.
辅酶 Q 和超氧化物在维生素 E 循环中的作用。
- DOI:
10.1007/978-1-4899-1789-8_20 - 发表时间:
1998 - 期刊:
- 影响因子:0
- 作者:
Valerian E Kagan;Y. Tyurina;Y. Tyurina;Eric Witt - 通讯作者:
Eric Witt
Deciphering of mitochondrial cardiolipin oxidative signaling in cerebral ischemia-reperfusion.
- DOI:
10.1038/jcbfm.2014.204. - 发表时间:
2015 - 期刊:
- 影响因子:
- 作者:
Jing Ji;Sophie Baart;Anna S Vikulina;Robert SB Clark;Tamil S Anthonymuthu;Vladimir A Tyurin;Lina Du;Claudette M St Croix;Yulia Y Tyurina;Jesse Lewis;Erin M Skoda;Anthony E Kline;Patrick M Kochanek;Peter Wipf;Valerian E Kagan;Hülya Bayır - 通讯作者:
lya Bayır
Sensitive and specific fluorescent probing of oxidative stress in different classes of membrane phospholipids in live cells using metabolically integrated cis-parinaric acid.
使用代谢整合的顺式石蜡油酸对活细胞中不同类别的膜磷脂中的氧化应激进行灵敏和特异的荧光探测。
- DOI:
- 发表时间:
1998 - 期刊:
- 影响因子:0
- 作者:
Valerian E Kagan;Vladimir B. Ritov;Y. Tyurina;V. Tyurin - 通讯作者:
V. Tyurin
Direct evidence for antioxidant effect of Bcl-2 in PC12 rat pheochromocytoma cells.
Bcl-2 在 PC12 大鼠嗜铬细胞瘤细胞中抗氧化作用的直接证据。
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:3.9
- 作者:
Y. Tyurina;V. Tyurin;Gianfranca Carta;P. Quinn;N. F. Schor;Valerian E Kagan - 通讯作者:
Valerian E Kagan
Reduction of phenoxyl radicals of the antitumour agent etoposide (VP-16) by glutathione and protein sulfhydryls in human leukaemia cells: Implications for cytotoxicity.
人类白血病细胞中谷胱甘肽和蛋白巯基减少抗肿瘤药物依托泊苷 (VP-16) 的苯氧基自由基:对细胞毒性的影响。
- DOI:
- 发表时间:
1996 - 期刊:
- 影响因子:3.2
- 作者:
J. Yalowich;Y. Tyurina;V. Tyurin;William P. Allan;Valerian E Kagan - 通讯作者:
Valerian E Kagan
Valerian E Kagan的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Valerian E Kagan', 18)}}的其他基金
Therapeutic targeting MDSC-mediated immune suppression in cancer
针对癌症中 MDSC 介导的免疫抑制的治疗
- 批准号:
10340589 - 财政年份:2021
- 资助金额:
$ 68.26万 - 项目类别:
Protein-Oxidized Phospholipid Interactions Determine Epithelial Cell Fate and Asthma Control
蛋白氧化磷脂相互作用决定上皮细胞命运和哮喘控制
- 批准号:
10593942 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
Selective Inhibitors of Pro-Ferroptotic Lipoxygenases - Next Generation Radiomitigators
促铁死亡脂氧合酶的选择性抑制剂 - 下一代放射减缓剂
- 批准号:
10176413 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
Selective Inhibitors of Pro-Ferroptotic Lipoxygenases - Next Generation Radiomitigators
促铁死亡脂氧合酶的选择性抑制剂 - 下一代放射减缓剂
- 批准号:
10408142 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
Protein-Oxidized Phospholipid Interactions Determine Epithelial Cell Fate and Asthma Control
蛋白氧化磷脂相互作用决定上皮细胞命运和哮喘控制
- 批准号:
10375454 - 财政年份:2020
- 资助金额:
$ 68.26万 - 项目类别:
The molecular basis of cardiolipin-protein interactions implicated in intrinsic apoptosis
心磷脂-蛋白质相互作用的分子基础涉及内在细胞凋亡
- 批准号:
9342976 - 财政年份:2016
- 资助金额:
$ 68.26万 - 项目类别:
Ferroptosis as a Death Mechanism in Lung Injury - Project 2
铁死亡作为肺损伤的死亡机制 - 项目 2
- 批准号:
10399560 - 财政年份:2014
- 资助金额:
$ 68.26万 - 项目类别:
NANOTOX 2014, 7th International Nanotoxicology Congress
NANOTOX 2014,第七届国际纳米毒理学大会
- 批准号:
8718354 - 财政年份:2014
- 资助金额:
$ 68.26万 - 项目类别:
Intra- and extra-cellular signaling by Cardiolipin in Lung injury
肺损伤中心磷脂的细胞内和细胞外信号传导
- 批准号:
8643330 - 财政年份:2014
- 资助金额:
$ 68.26万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 68.26万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 68.26万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 68.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 68.26万 - 项目类别:
Studentship














{{item.name}}会员




