A deubiquitination module controls Treg adaptation to tumor microenvironment
去泛素化模块控制 Treg 对肿瘤微环境的适应
基本信息
- 批准号:10545001
- 负责人:
- 金额:$ 55.21万
- 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:2021-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcidityAmino AcidsAntitumor ResponseCancer PatientCarbon DioxideClinicalCuesDataDeubiquitinationDevelopmentFOXP3 geneGlucoseGrowth FactorHumanHypoxiaImmune systemImmunosuppressionImmunotherapyInfiltrationMalignant neoplasm of lungMediatingMetabolicModelingMolecularMusNeoplasm MetastasisPeptide HydrolasesPublicationsRegulatory T-LymphocyteRoleStressTestingTherapeuticTreatment EfficacyTumor EscapeTumor ImmunityUbiquitinUp-Regulationanti-tumor immune responsecancer cellcancer therapycheckpoint receptorscytokineeffector T cellfitnessforkhead proteinimmune checkpoint blockadeimmunogenicityimprovedneoplasm immunotherapyneoplastic cellnovelprogramssuccesssynergismtranscription factortumortumor microenvironmentubiquitin isopeptidase
项目摘要
Project Summary:
One of the recent advances in cancer treatment is the development of immunotherapy largely
through targeting the checkpoint receptors. However, attempts at immunotherapy to increase
antitumor immune responses have achieved very limited success. A major hurdle in tumor
immunotherapy is mediated by regulatory T (Treg) cells, which suppress the function of antitumor
effector T cells. The lineage transcription factor Forkhead Box P3 (FoxP3) is known as a
programmer for Treg adaptation in the harsh tumor microenvironment such as metabolic changes
and hypoxia. However, the factors that control FoxP3-mediated Treg fitness to orchestrate the
survival and functions of intratumoral Treg cells have not been identified. Importantly, our recent
publications and preliminary discoveries in the current application suggest that tumor
microenvironment factors possibly induce Treg fitness/adaptation through selectively
upregulating a deubiquitinase module, including USP21 and USP22, but not USP7, of FoxP3 to
control Treg adaptation. The current proposed studies will identify the tumor microenvironment
factors that induce USP21 and USP22 expression in Tregs (Aim 1), and to test whether Tregs
with simultaneous USP21 and USP22 deletion fail to adapt in the harsh tumor microenvironment,
which consequently potentiates the antitumor immune therapy (Aim 2). Results from our proposed
study will define a novel molecular cue in control Treg fitness to the tumor microenvironment and
provide a rationale for the combined USP21 and USP22 suppression in antitumor immune therapy.
项目总结:
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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Deyu Fang其他文献
Deyu Fang的其他文献
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{{ truncateString('Deyu Fang', 18)}}的其他基金
VPS72 controls Treg cell stability and adaptation to tumor microenvironment
VPS72 控制 Treg 细胞稳定性和对肿瘤微环境的适应
- 批准号:
10754017 - 财政年份:2023
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10666589 - 财政年份:2022
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$ 55.21万 - 项目类别:
A deubiquitination module controls Treg adaptation to tumor microenvironment
去泛素化模块控制 Treg 对肿瘤微环境的适应
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Regulation of Rhythmic m6A RNA Modification by ER‐associated Degradation
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- 资助金额:
$ 55.21万 - 项目类别:
A deubiquitination module controls Treg adaptation to tumor microenvironment
去泛素化模块控制 Treg 对肿瘤微环境的适应
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10320965 - 财政年份:2021
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Regulation of Rhythmic m6A RNA Modification by ER‐associated Degradation
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- 资助金额:
$ 55.21万 - 项目类别:
Targeting a Treg deubiquitinase in antitumor immune therapy
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