Delineating the mechanisms by which tumor immunity multicellular networks shape T cell state
描述肿瘤免疫多细胞网络塑造 T 细胞状态的机制
基本信息
- 批准号:10662688
- 负责人:
- 金额:$ 22.66万
- 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:2023-08-23 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcademiaAdvisory CommitteesAntigensAntitumor ResponseAreaB-LymphocytesBehaviorBiologicalBiological AssayBiologyBlood VesselsCD8-Positive T-LymphocytesCXCL10 geneCXCL11 geneCXCL13 geneCancer PatientCell CommunicationCellsChronicColorectal CancerCommunicationDataData SetDevelopment PlansEnvironmentEnvironmental Risk FactorFacultyFeedbackGeneral HospitalsGenesGrantHumanHybridsHypoxiaImmuneImmunityImmunotherapyIn Situ HybridizationInterferon Type IIInterferonsInvestigationLaboratoriesLeadershipLigandsMalignant - descriptorMalignant NeoplasmsMalignant neoplasm of lungMapsMassachusettsMentorsMentorshipMicroscopyMismatch RepairMismatch Repair DeficiencyMoldsMorphologyNeighborhoodsPD-1 blockadePathologistPathologyPathway interactionsPatientsPhenotypePhysiciansPopulationPositioning AttributePostdoctoral FellowProcessProfessional CompetenceRNARecording of previous eventsRecurrenceResearchResearch ProposalsRoleSamplingScientistSeriesShapesSpecimenStructureT cell responseT-Cell ActivationT-Cell ProliferationT-LymphocyteTechnical ExpertiseTherapeuticTissuesTrainingTumor ImmunityWritinganti-tumor immune responsecancer cellcancer therapycareer developmentcell behaviorcell typechemokineclinically significantcombatexhaustexhaustionfightinghuman DNAimprovedin vitro testinginstructorlymph nodesprogramsrecruitresponseskillsstemtranscriptomicstranslational potentialtumortumor immunology
项目摘要
T cells are greatly impacted by their environment, interacting with neighboring cells that may attract,
stimulate, inhibit, and otherwise alter T cell activity. Examining multicellular tissue organization is thus required
for unraveling the T cell anti-tumor response. Yet, little is known about what multicellular networks exist in
cancer, how they are organized, and how they modulate T cell activity. This project explores the mechanistic
basis of a tumor immunity multicellular network (hub) discovered in the candidate’s (Dr. Jonathan Chen) recent
single cell transcriptomic study of human colorectal cancer. The objective of this proposal is to investigate the
composition, spatial organization and function of this immunity hub in relation to the anti-tumor T cell response.
This proposal aims to (1) spatially map cellular interactions in the immunity hub that may shape T cell behavior
and (2) identify environmental factors in the immunity hub shaping CXCL13+ CD8 T cell state and uncover the
role of CXCL13 in CRC. The candidate anticipates these studies will demonstrate that the newly discovered
tumor immunity multicellular network recruits tumor-specific T cells, and that multiple cell types within the hub
participate in shaping the state of these T cells. Furthermore, this investigation of the immunity hub is likely to
identify promising strategies for therapeutic manipulation.
The candidate, Dr. Jonathan Chen, is currently a postdoc in the lab of Dr. Nir Hacohen and an
Instructor in the Department of Pathology of the Massachusetts General Hospital. The proposal incorporates
specific technical skills that will be required for the project, including training in analysis of ultra-highplex RNA
in situ hybridization datasets. The structured career development plan includes training and mentorship in
laboratory management, scientific leadership, research communication, grant writing, and other critical career
skills. These technical and career skills will be acquired under the guidance of Dr. Nir Hacohen, who will serve
as primary mentor and has a history of trainees obtaining faculty positions in academia, and Dr. Eli Van Allen
as computational co-mentor. A Research Advisory Committee of world-class scientists including Drs. Arlene
Sharpe, David Rimm, and David Ting will provide additional support and guidance. Through this
comprehensive program, the candidate will acquire a unique set of research skills that will enable him to
transition to an independent physician-scientist faculty position with a lab focused on basic mechanisms and
therapeutic opportunities in cancer immunology.
T细胞受到环境的极大影响,与相邻细胞相互作用,
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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Jonathan Howard Chen其他文献
Jonathan Howard Chen的其他文献
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- 批准号:
0451289 - 财政年份:2005
- 资助金额:
$ 22.66万 - 项目类别:
Standard Grant














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