Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
基本信息
- 批准号:10625967
- 负责人:
- 金额:$ 52.11万
- 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:2021-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAerodigestive TractAgingAntigen PresentationAntigensArchitectureCD8-Positive T-LymphocytesCancerousCarcinogensCarcinomaCellsClinical ResearchClonal ExpansionComplementDevelopmentElderlyEnvironmental CarcinogensEpithelial CellsEpitheliumExposure toFoundationsGoalsHead and Neck CancerHealthHomeostasisHumanHuman PapillomavirusHyperplasiaImmuneImmune responseImmune signalingImmune systemImmunityImmunocompetentImmunologic FactorsIndividualLesionLow risk HPVMaintenanceMalignant - descriptorMalignant NeoplasmsMediatingModelingMolecularMucous MembraneMusMutateMutationNatureNormal tissue morphologyOral mucous membrane structureOutcomeOutcomes ResearchPapillomavirusPatientsPatternPersonsPlayProcessProliferatingResearchRiskRoleSkinSkin CancerSkin CarcinogenesisSkin colonizationT cell responseT-Cell ActivationT-Cell DepletionT-LymphocyteTestingTissuesTreatment CostUV carcinogenesisUV inducedUltraviolet RaysUnited StatesVaccinationViralViral AntigensVirusWorkantiviral immunitycancer cellcancer preventioncancer therapycarcinogenesiscarcinogenicitycell injurychemokinecommensal bacteriacytokinehead and neck cancer patienthigh riskhuman viromeimprovedinnate immune pathwaysinnovationmicrobiomemouse modelmucosal sitenormal microbiotanovelnovel strategiespremalignantpreventprotective effectreproductive tracttranscriptome sequencingtumorultravioletvirome
项目摘要
Project Summary/Abstract:
Research in the field of microbiome has largely focused on the beneficial effects of commensal bacteria in
regulating tissue homeostasis and the immune responses. However, a commensal role for virome in supporting
human health has not been explored. We propose to investigate the commensal virome and its beneficial impact
on tissue homeostasis and cancer protection in barrier epithelia. Informed by our recent discovery of the
beneficial role of low-risk commensal papillomaviruses and the immunity against them in protecting the skin
against carcinogen-driven cancer, we propose a completely novel approach to prevent nonviral cancers by using
the patients’ own virome and the immune system to precisely target early malignant clones within the barrier
epithelia. In particular, the widespread presence of commensal human papillomaviruses (HPVs) in barrier
epithelia and the ability of a competent immune system in adults to control these viruses will provide a unique
opportunity to determine the interplay of commensal viruses, epithelial tumors and the immune system. To
accomplish this, we will use novel mouse models of papillomavirus colonization to (1) determine the impact of
commensal HPVs on maintaining the homeostasis of epithelium exposed to environmental carcinogens, (2)
identify the innate immune factors that are required for the activation of antiviral T cells targeting malignant cells
while spare the virus-positive normal tissue, and (3) determine the role of papillomaviruses that colonize the oral
mucosa on the carcinogen-induced head and neck cancer. The outcomes of the proposed research will establish
a fundamental role for commensal virome in combating the early stages of cancer development and provide the
means to prevent and treat nonviral epithelial cancers using patients’ own virome and the immune cells.
项目摘要/摘要:
微生物组领域的研究主要集中在共生细菌的有益作用上
调节组织稳态和免疫反应。然而,病毒组在支持
人类健康尚未被探索。我们建议研究共生病毒组及其有益影响
关于屏障上皮的组织稳态和癌症保护。根据我们最近的发现
低风险共生乳头瘤病毒及其免疫力在保护皮肤方面的有益作用
针对致癌物驱动的癌症,我们提出了一种全新的方法来预防非病毒性癌症
患者自身的病毒组和免疫系统可以精确地瞄准屏障内的早期恶性克隆
上皮细胞。特别是,屏障中广泛存在共生人乳头瘤病毒(HPV)
上皮细胞和成人强大的免疫系统控制这些病毒的能力将提供独特的
确定共生病毒、上皮肿瘤和免疫系统之间相互作用的机会。到
为了实现这一目标,我们将使用乳头瘤病毒定植的新型小鼠模型来(1)确定
共生 HPV 维持暴露于环境致癌物的上皮细胞的稳态,(2)
识别激活针对恶性细胞的抗病毒 T 细胞所需的先天免疫因子
同时保留病毒阳性的正常组织,以及(3)确定定植于口腔的乳头瘤病毒的作用
粘膜上的致癌物质诱发头颈癌。拟议研究的结果将确定
共生病毒组在对抗癌症发展的早期阶段中发挥着重要作用,并提供
是指利用患者自身的病毒组和免疫细胞来预防和治疗非病毒性上皮癌。
项目成果
期刊论文数量(2)
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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Shadmehr Demehri其他文献
Shadmehr Demehri的其他文献
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{{ truncateString('Shadmehr Demehri', 18)}}的其他基金
Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
- 批准号:
10397664 - 财政年份:2021
- 资助金额:
$ 52.11万 - 项目类别:
Immunity to commensal papillomaviruses for cancer therapy
对共生乳头瘤病毒的免疫用于癌症治疗
- 批准号:
10209691 - 财政年份:2021
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
9973215 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10633109 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10617947 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10228570 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10844016 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Immunotherapy for Skin Cancer Precursors to Prevent Skin Cancer
针对皮肤癌前体的免疫疗法可预防皮肤癌
- 批准号:
10413211 - 财政年份:2019
- 资助金额:
$ 52.11万 - 项目类别:
Epithelium-derived alarmins role in breast cancer immunoprevention
上皮源性警报素在乳腺癌免疫预防中的作用
- 批准号:
10468153 - 财政年份:2018
- 资助金额:
$ 52.11万 - 项目类别:
Epithelium-derived alarmins role in breast cancer immunoprevention
上皮源性警报素在乳腺癌免疫预防中的作用
- 批准号:
9788324 - 财政年份:2018
- 资助金额:
$ 52.11万 - 项目类别:
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