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Core B: Animal Model and Immunotyping Core

Core B: Animal Model and Immunotyping Core
核心 B:动物模型和免疫分型核心
批准号:
10704234
负责人:
THOMAS A. HAMILTON
金额:
$38.49万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-09-13 至 2027-08-31
关键词:
AddressAffectAnimal ModelAutologousBioinformaticsCD8-Positive T-LymphocytesCancer ModelCell surfaceCellsChargeConsultationsCrossbreedingCytokine Network PathwayCytokine SignalingDataData AnalysesDendritic CellsDetectionDissectionDoseEnsureFibroblastsFlow CytometryFluorescence-Activated Cell SortingFosteringGenetically Engineered MouseGoalsGrowthHead and Neck Squamous Cell CarcinomaHumanIL17 geneImmuneImmune checkpoint inhibitorImmunocompetentImmunocompromised HostImmunotherapyIndividualInflammationInflammatoryInfrastructureInterferon-betaInterferonsKRASG12DKineticsKnock-in MouseLibrariesLung AdenocarcinomaMalignant NeoplasmsMalignant neoplasm of lungMeasuresMissionModelingMolecularMouse StrainsMusMyeloid CellsOutcomePathway interactionsPeripheral Blood Mononuclear CellProceduresProtocols documentationResearch PersonnelResistanceRoleSTAT2 geneSamplingServicesShapesSignal PathwayStandardizationSting InjurySuspensionsTestingTh1 CellsTherapeuticTissuesTranscendTransforming Growth Factor betaTumor BiologyTumor Cell LineTumor ImmunityTumor PromotionTumor TissueWorkXenograft Modelcancer typecell typecheckpoint therapychemotherapycytokinedesignexperienceexperimental studyfluorophorehumanized mouseimmune checkpoint blockadeimprovedin vivoinflammatory milieuinstrumentationmembermouse modelnovel therapeutic interventionpatient derived xenograft modelpre-clinicalpre-clinical assessmentprogramsresponsesingle cell sequencingtissue preparationtooltranscriptome sequencingtranscriptomicstreatment responsetriple-negative invasive breast carcinomatumortumor microenvironmenttumor progressiontumor xenograft

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英文摘要
Project Summary Our preliminary data suggested a shared paradigm for the impact of the STING-IFN-β/TGFβ/IL-17 cytokine network on tumor progression and responses to therapy, which transcends the tissue origins of each cancer. Our goal, to unravel the crosstalk and define the paradigms, necessitates standardization of the protocols and procedures used by each constituent project, in order to unify our approaches in establishing preclinical tumor models and measuring tumor responses to therapy. Our ability to reach meaningful conclusions critically hinges on comparable execution of in vivo studies. Furthermore, a common readout shared by all three constituent projects is the inflammatory status in the TME. While immune-supportive inflammation (CD8, Th1, and dendritic cells) is associated with favorable responses to immune checkpoint inhibitor therapy, an immune-suppressive inflammatory environment (immature myeloid cells and fibroblasts) can antagonize anti-tumor immunity. Accurate detection, characterization and quantification of multiple cell types by flow cytometry and single-cell sequencing are crucial for assessing the state of intra-tumoral inflammation. A shared infrastructure that enables reliable analysis of the TME is essential for studying cytokine crosstalk. Taken together, the Animal Model and Immunotyping Core will be charged with two missions. First, the Core will provide technical and experimental infrastructure to enable uniform and standard in vivo analyses, including preclinical assessment of cancer therapeutics and characterization of the TME. Secondly, the Core will function as a hub for interaction among the constituent projects, including analytics assistance and scientific consultation on analyses of the TME.
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IL-17-driven mechanisms for tumor progression and resistance to therapies
  • 批准号:
    10704232
  • 项目类别:
  • 资助金额:
    $51.26万
  • 财政年份:
    2022
  • 负责人:
    THOMAS A. HAMILTON
  • 依托单位:
STAT6 and IL-4/IL-13 Dependent Gene Expression
  • 批准号:
    6942226
  • 项目类别:
  • 资助金额:
    $21.07万
  • 财政年份:
    2004
  • 负责人:
    THOMAS A. HAMILTON
  • 依托单位:
Mechanisms of Macrophage Activation
  • 批准号:
    6577347
  • 项目类别:
  • 资助金额:
    $28.76万
  • 财政年份:
    2003
  • 负责人:
    THOMAS A. HAMILTON
  • 依托单位:
Mechanisms of Macrophage Activation
  • 批准号:
    6922790
  • 项目类别:
  • 资助金额:
    $28.76万
  • 财政年份:
    2003
  • 负责人:
    THOMAS A. HAMILTON
  • 依托单位:
海外基金