Paradoxical roles of tumor lymphangiogenesis on tumor immunity and implications for immunotherapy - Resubmission 01
肿瘤淋巴管生成对肿瘤免疫的矛盾作用及其对免疫治疗的影响 - 重新提交 01
基本信息
- 批准号:10368055
- 负责人:
- 金额:$ 36.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAntigensAutomobile DrivingBindingBioinformaticsBiophysicsBlocking AntibodiesBloodCCL21 geneCell CompartmentationCell SurvivalCellsClinical ResearchDataDendritic Cell VaccineDendritic CellsDevelopmentEnvironmentEpitope spreadingGrowth FactorHomingHumanImmuneImmune checkpoint inhibitorImmunityImmunosuppressionImmunotherapyInfiltrationInflammatoryLymphangiogenesisLymphaticLymphatic SystemLymphoidMalignant NeoplasmsMemoryModelingMusNeoplasm MetastasisPatientsPhenotypePlayPredispositionPrognosisProspective StudiesProteinsReportingResearchResistanceRoleRouteSerumShapesSideSignal TransductionSpecificityStructureT cell therapyT memory cellT-Cell ActivationT-LymphocyteT-cell inflamedTherapeuticTissuesTumor ImmunityTumor-infiltrating immune cellsUp-RegulationVaccinationVaccinesValidationVariantVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3beta catenincancer immunotherapycell killingchemokinecytokineefficacy evaluationimmune checkpoint blockadeimmunogeniclymph nodeslymphatic vesselmelanomamouse modelnanoparticleneoplastic cellnovelnovel therapeutic interventionoverexpressionpredicting responseprogramsreceptorrecruitresponsetranslational applicationstranslational potentialtumortumor microenvironmenttumor progressiontumor-immune system interactionsvaccine strategy
项目摘要
Project Summary
In melanoma and other cancers, the expansion of the local lymphatic network via expression of VEGF-C in the
tumor microenvironment promotes metastasis and is widely correlated with poor prognosis. We and others
have shown that VEGF-C-activated lymphatic vessels play important immune suppressive roles in the tumor
microenvironment. Paradoxically, we have observed that in mouse melanoma models, lymphangiogenic tu-
mors were more responsive to immunotherapy, including in adoptive T cell therapy, dendritic cell vaccines, and
protein vaccination. Here we propose a research program that explores this other side of tumor lymphangio-
genesis, and suggest a novel hypothesis that while VEGF-C in the tumor microenvironment can induce in-
flammation and immune suppression, it also enhances the infiltration of naïve T cell infiltration, at least in part
by upregulating the lymphoid homing chemokine CCL21. This enhanced infiltration, in turn, can prime the tu-
mor for enhanced responsiveness to immunotherapy. Three aims are proposed to explore (i) validation and
mechanistic underpinnings in mouse models, (ii) relevance to human melanoma, and (iii) translational applica-
tion.
项目摘要
在黑色素瘤和其他癌症中,通过VEGF-C在淋巴结中的表达,局部淋巴网络的扩张是通过淋巴结转移来实现的。
肿瘤微环境促进转移并与不良预后广泛相关。我们和其他人
VEGF-C激活的淋巴管在肿瘤中发挥重要的免疫抑制作用
微环境。奇怪的是,我们已经观察到,在小鼠黑色素瘤模型中,淋巴管生成性肿瘤-
MORS对免疫治疗更有反应,包括过继性T细胞治疗、树突状细胞疫苗和
蛋白质疫苗在这里,我们提出了一个研究计划,探索肿瘤淋巴管的另一面-
并提出了一种新的假设,即肿瘤微环境中的VEGF-C可以诱导肿瘤的发生,
炎症和免疫抑制,它也增强了幼稚T细胞的浸润,至少部分
通过上调淋巴归巢趋化因子CCL 21这种增强的渗透,反过来,可以启动你-
莫尔用于增强对免疫疗法的反应性。提出了三个目标,以探讨(一)验证和
小鼠模型中的机制基础,(ii)与人黑色素瘤的相关性,以及(iii)翻译应用。
是的。
项目成果
期刊论文数量(22)
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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Melody Ann Swartz其他文献
Melody Ann Swartz的其他文献
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{{ truncateString('Melody Ann Swartz', 18)}}的其他基金
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10457432 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10696126 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10299447 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10533678 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10737791 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Probing cellular, molecular and biomechanical barriers to immunotherapy in the tumor microenvironment with organotypic in vitro models of the tumor-lympho-immune interface
利用肿瘤-淋巴-免疫界面的器官型体外模型探索肿瘤微环境中免疫治疗的细胞、分子和生物力学障碍
- 批准号:
10681942 - 财政年份:2021
- 资助金额:
$ 36.32万 - 项目类别:
Paradoxical roles of tumor lymphangiogenesis on tumor immunity and implications for immunotherapy - Resubmission 01
肿瘤淋巴管生成对肿瘤免疫的矛盾作用及其对免疫治疗的影响 - 重新提交 01
- 批准号:
9891035 - 财政年份:2018
- 资助金额:
$ 36.32万 - 项目类别:
Immunomodulatory roles of lymphatic vessels in allergic airway inflammation
淋巴管在过敏性气道炎症中的免疫调节作用
- 批准号:
9300618 - 财政年份:2017
- 资助金额:
$ 36.32万 - 项目类别:
2014 Molecular Mechanisms in Lymphatic Function and Disease Gordon Research Confe
2014年淋巴功能与疾病的分子机制戈登研究会议
- 批准号:
8718874 - 财政年份:2014
- 资助金额:
$ 36.32万 - 项目类别:
Lymph vs. blood angiogenesis: functional differences
淋巴与血管生成:功能差异
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6710442 - 财政年份:2003
- 资助金额:
$ 36.32万 - 项目类别:
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