Neuro-Immune Interaction in Cancer Development
癌症发展中的神经免疫相互作用
基本信息
- 批准号:10686625
- 负责人:
- 金额:$ 19.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAccelerationAdaptive Immune SystemAdrenergic AgentsAnimalsAutoimmunityB-LymphocytesBreast Cancer ModelBreast Cancer PatientCD8-Positive T-LymphocytesCalcitonin Gene-Related PeptideCalcitonin-Gene Related Peptide ReceptorCancer EtiologyCell physiologyCellsCessation of lifeComplexDevelopmentEsthesiaExhibitsGeneticGoalsGrowthHumanImmuneImmune responseImmune systemImmunotherapeutic agentImmunotherapyIndividualInfectionInfiltrationInflammatoryInvestigationLaboratoriesMalignant NeoplasmsMammary Gland ParenchymaMammary NeoplasmsMapsMeasuresMediatingMentorsModelingMusNeoplasm MetastasisNeoplasm TransplantationNerveNerve FibersNeuraxisNeuroimmuneNeuronsNeuropeptide ReceptorNeuropeptidesNeurotransmittersNeutrophil ActivationOklahomaPainPathway interactionsPatientsPharmaceutical PreparationsPharmacologyPhenotypePlayPopulationPredispositionPrognosisPropertyRag1 MouseRoleSecondary toSensorySignal TransductionSiteSkinSolid NeoplasmSubstance PSubstance P ReceptorT cell responseT-Cell ProliferationT-LymphocyteTRPV1 geneTestingTumor ImmunityTumor-infiltrating immune cellsWomanWorkadaptive immune responseadaptive immunityafferent nerveanti-PD-1anti-tumor immune responseantitumor effectcell growthchemotherapycytotoxicdraining lymph nodehuman diseaseimmune functionimprovedinhibitorlymph flowmalignant breast neoplasmmigrationneoplastic cellnerve supplyneurotransmissionnovelpathogenic bacteriapeptide Pprogrammed cell death protein 1receptorresponsesecondary lymphoid organtherapeutic evaluationtranslational cancer researchtumortumor growthtumor microenvironmenttumorigenesis
项目摘要
While the presence of nerves in solid tumors has been observed for hundreds of years, investigation of the
impact of these nerves on tumor growth has only been initiated in the last 10 years. The bulk of this work has
focused on the impact of neurotransmitters on tumor cell growth and metastasis, however immune cells also
express receptors for a wide variety of neurotransmitters, which can have immune-activating and immuneinhibiting
properties. In preliminary studies using a murine breast cancer model, we have found that the
presence of sensory nerves is necessary for tumor inhibition by the adaptive immune system. Furthermore,
blockade of a specific neurotransmitter produced by sensory nerves, calcitonin gene related peptide (CGRP)
inhibited tumor growth and improved T cell infiltration into tumors, suggesting both pro- and anti-tumor
activities for sensory nerves in breast cancer. In this project, we will decipher how sensory nerves promote
adaptive immune responses to tumors. We will also investigate the mechanism by which CGRP inhibition
improves tumor control, and whether this treatment can synergize with anti-PD-1 immunotherapy. Finally, we
will evaluate whether presence of sensory nerves, adrenergic nerves, or specific neurotransmitters including
CGRP correlate with immune infiltration and response to chemotherapy in breast cancer patients. Overall
these studies will provide critical information on a potentially novel immunotherapeutic pathway that can be
modulated in patients to promote tumor control.
虽然实体瘤中神经的存在已经被观察了数百年,但对神经的研究
这些神经对肿瘤生长的影响直到最近十年才开始出现。这项工作的大部分内容是
重点关注神经递质对肿瘤细胞生长和转移的影响,但免疫细胞也
表达多种神经递质的受体,这些神经递质可以具有免疫激活和免疫抑制作用
特性。在使用小鼠乳腺癌模型的初步研究中,我们发现
感觉神经的存在对于适应性免疫系统抑制肿瘤是必要的。此外,
阻断感觉神经产生的特定神经递质,降钙素基因相关肽(CGRP)
抑制肿瘤生长并改善 T 细胞对肿瘤的浸润,表明其具有促肿瘤和抗肿瘤作用
乳腺癌中感觉神经的活动。在这个项目中,我们将破译感觉神经如何促进
对肿瘤的适应性免疫反应。我们还将研究 CGRP 抑制的机制
改善肿瘤控制,以及这种治疗是否可以与抗 PD-1 免疫疗法产生协同作用。最后,我们
将评估是否存在感觉神经、肾上腺素能神经或特定神经递质,包括
CGRP 与乳腺癌患者的免疫浸润和化疗反应相关。全面的
这些研究将提供关于潜在的新型免疫治疗途径的关键信息,该途径可以
对患者进行调节以促进肿瘤控制。
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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Maureen Cox其他文献
Maureen Cox的其他文献
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{{ truncateString('Maureen Cox', 18)}}的其他基金
Nervous system control of immunity to C. difficile
神经系统对艰难梭菌免疫的控制
- 批准号:
10625177 - 财政年份:2023
- 资助金额:
$ 19.73万 - 项目类别:
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