Systems Biology of Tumor-Immune-Stromal Interactions in Metastatic Progression
转移进展中肿瘤-免疫-基质相互作用的系统生物学
基本信息
- 批准号:10729464
- 负责人:
- 金额:$ 191.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-19 至 2028-08-31
- 项目状态:未结题
- 来源:
- 关键词:Adaptive Immune SystemAddressAdvanced DevelopmentAffectAnatomyArchivesAreaBindingBiologicalBiological MarkersCancer EtiologyCancer PatientCellsCessation of lifeClinicalCollaborationsCommunitiesComplexComputer AnalysisComputing MethodologiesDataData SetDedicationsDevelopmentDiseaseDistantDistant MetastasisEnsureEventFundingGenerationsGenomicsGoalsHead and Neck CancerHomeostasisHumanImageImaging technologyImmuneImmune ToleranceImmune systemImmunologyImmunosuppressionIn SituInvadedKineticsKnowledgeLung AdenocarcinomaMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of lungMediatingMediatorMetastatic Neoplasm to Lymph NodesMethodologyMethodsMusNatureNeoplasm MetastasisOutcomePatientsPilot ProjectsPopulationPredispositionPrimary NeoplasmProcessProteomicsRecordsResearchResearch PersonnelResearch Project GrantsResource SharingRoleSamplingSeriesSiteSolidSolid NeoplasmStromal CellsStromal NeoplasmSystemSystems BiologyTechnologyTherapeuticTissuesTumor BiologyTumor Immunityanalytical toolanticancer researchbiocomputingcancer cellcell typecohortcommunity engagementdata integrationdata managementdraining lymph nodehigh dimensionalityimmune clearancein situ imaginginsightinterdisciplinary approachlymph nodeslymphatic drainagemembermigrationmouse modelmultidisciplinarymultimodalitymultiscale dataneoplastic cellnext generationnoveloutreachpre-clinicalpreventrecruitrepositorysingle cell technologysingle-cell RNA sequencingspatiotemporaltechnology platformtooltranscriptomicstreatment planningtreatment responsetumortumor progression
项目摘要
ABSTRACT/SUMMARY – Overall
Distant metastasis is the primary cause of cancer-related death. To colonize distant tissues, cancer cells must
migrate while evading elimination by the immune system. Evidence suggests that key steps in the induction
process of immune tolerance occur early in the metastatic cascade, located at the regional lymph nodes proximal
to the primary tumor site. However, the nature of the interactions between malignant, immune and stromal cells
remains poorly understood, including those that involve metastatic cells within the lymph nodes. Even though
lymph nodes are in fact commonly assessed in cancer patients to determine disease stage and treatment plan,
they are understudied in the context of metastatic progression. To fill this scientific knowledge gap, we propose
a Research Center to unravel the role of lymph nodes in metastatic progression. We have established that lymph
node metastasis constitutes an essential, first step in the metastatic cascade of cancer progression. We have
found that such metastases act locally upon the adaptive immune system within the lymph nodes to begin to
induce systemic tolerance of the tumor. We will further explore this new paradigm of metastases in two
malignancies, head and neck cancer and lung adenocarcinoma, by focusing on the kinetics and spatiotemporal
changes at the primary tumor, lymph node and distant sites, associated with the onset and progression of
metastasis. We have assembled a multidisciplinary team whose coordinated efforts will involve the application
of genomic and single-cell in-situ imaging technologies on preclinical and human samples to explore the
evidence and mechanisms of the induction of immunosuppression in the lymph nodes. We propose two
Research Projects that focus our scientific theme on lymph node metastasis by analyzing kinetics in a mouse
model (Project 1) and spatial temporal changes in samples of lymph nodes and their concurrent primary tumor
(Project 2), inter-connected through integrative computational analyses. Both projects will utilize a shared
resource core dedicated to the acquisition of patient samples and associated clinical annotation and data
management (Biospecimen Core and Data Core). These efforts will yield highly multiplexed, multi-scale datasets
which will be analyzed by novel bio-computational methods to reconstruct intracellular and intercellular molecular
interaction networks in order to identify, then functionally validate, critical mediators of metastasis. Our ultimate
objective is to advance our understanding of the systemic consequences of lymph node metastases and identify
new biomarkers and therapeutic approaches. Our Research Center is also dedicated to promoting our early
investigators as the next generation thought leaders applying principles of systems biology to the study of
metastasis. Our Outreach Core activity will ensure that our Research Center’s scientific and methodological
advances in applying the principles of cancer systems biology toward the study of tumor-immune-stromal
interactions are fully disseminated in the cancer research and broader communities.
摘要/摘要-总体
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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EDGAR G. ENGLEMAN其他文献
EDGAR G. ENGLEMAN的其他文献
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{{ truncateString('EDGAR G. ENGLEMAN', 18)}}的其他基金
Project 3: Impact of tumor genetics on PDAC immunobiology and responses to macrophage-targeted immunotherapy
项目 3:肿瘤遗传学对 PDAC 免疫生物学的影响以及对巨噬细胞靶向免疫治疗的反应
- 批准号:
10704089 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Targeting Lymph Node Dependent Immune Tolerance in Cancer
针对癌症中的淋巴结依赖性免疫耐受
- 批准号:
10210557 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Innate Immune Mechanisms Contributing to Cancer Growth in Obesity
肥胖导致癌症生长的先天免疫机制
- 批准号:
10654802 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Innate Immune Mechanisms Contributing to Cancer Growth in Obesity
肥胖导致癌症生长的先天免疫机制
- 批准号:
10430268 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Innate Immune Mechanisms Contributing to Cancer Growth in Obesity
肥胖导致癌症生长的先天免疫机制
- 批准号:
10278250 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Project 3: Impact of tumor genetics on PDAC immunobiology and responses to macrophage-targeted immunotherapy
项目 3:肿瘤遗传学对 PDAC 免疫生物学的影响以及巨噬细胞靶向免疫治疗的反应
- 批准号:
10456771 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Innate Immune Mechanisms Contributing to Cancer Growth in Obesity
肥胖导致癌症生长的先天免疫机制
- 批准号:
10706825 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Project 3: Impact of tumor genetics on PDAC immunobiology and responses to macrophage-targeted immunotherapy
项目 3:肿瘤遗传学对 PDAC 免疫生物学的影响以及对巨噬细胞靶向免疫治疗的反应
- 批准号:
10187127 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
Targeting Lymph Node Dependent Immune Tolerance in Cancer
针对癌症中的淋巴结依赖性免疫耐受
- 批准号:
10366092 - 财政年份:2021
- 资助金额:
$ 191.91万 - 项目类别:
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