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
癌症中髓样区室的显著变化是病理激活的
具有有效抑制免疫反应能力的未成熟骨髓细胞-骨髓来源的抑制细胞
(MDSC)。在荷瘤小鼠中,MDSC的总群体由三组细胞组成:
丰富(>75%)未成熟的病理活化中性粒细胞(PMN-MDSC);不太丰富(<20%)
病理活化单核细胞(M-MDSC)群体;和早期髓系造血干细胞(<5%)群体
前体在肿瘤微环境中,MDSC比外周淋巴细胞更具有免疫抑制作用。
器官.然而,这一现象的机制仍然相当难以捉摸。我们知识的差距在于
了解MDSC在肿瘤中的功能调节机制及其对MDSC的特殊要求,
面向.在这个提议中,我们将检验肿瘤中存在不同MDSC群体的假设。这些
群体可以通过特定的标记物来定义,最重要的是,对铁凋亡细胞具有不同的敏感性。
死亡决定了它们的功能活动。我们将测试在PMN-MDSC中靶向铁凋亡的概念,
可能会对免疫反应产生功能性影响。这个项目的目标是揭示
调节肿瘤中骨髓细胞功能的机制,并开发新的方法来调节肿瘤中骨髓细胞的功能。
癌症的免疫反应
本研究的具体目的如下:(1)探讨铁中毒介导的免疫机制
PMN-MDSC在肿瘤中诱导的抑制作用;(2)研究靶向治疗的潜力
PMN-MDSC中的铁凋亡。
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)
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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
beta-Carotene. An antioxidant or a target of oxidative stress in cells?
β-胡萝卜素。
- DOI:
- 发表时间:
1998 - 期刊:
- 影响因子:0
- 作者:
Billy W. Day;Stefania Bergamini;Y. Tyurina;Gianfranca Carta;V. Tyurin;Valerian E Kagan - 通讯作者:
Valerian E Kagan
Valerian E Kagan的其他文献
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{{ 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:
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