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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：
Maureen Cox
金额：
$ 19.73万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
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：
https://reporter.nih.gov/project-details/10686625
关键词：
Ablation Acceleration Adaptive Immune System Adrenergic Agents Animals Autoimmunity B-Lymphocytes Breast Cancer Model Breast Cancer Patient CD8-Positive T-Lymphocytes Calcitonin Gene-Related Peptide Calcitonin-Gene Related Peptide Receptor Cancer Etiology Cell physiology Cells Cessation of life Complex Development Esthesia Exhibits Genetic Goals Growth Human Immune Immune response Immune system Immunotherapeutic agent Immunotherapy Individual Infection Infiltration Inflammatory Investigation Laboratories Malignant Neoplasms Mammary Gland Parenchyma Mammary Neoplasms Maps Measures Mediating Mentors Modeling Mus Neoplasm Metastasis Neoplasm Transplantation Nerve Nerve Fibers Neuraxis Neuroimmune Neurons Neuropeptide Receptor Neuropeptides Neurotransmitters Neutrophil Activation Oklahoma Pain Pathway interactions Patients Pharmaceutical Preparations Pharmacology Phenotype Play Population Predisposition Prognosis Property Rag1 Mouse Role Secondary to Sensory Signal Transduction Site Skin Solid Neoplasm Substance P Substance P Receptor T cell response T-Cell Proliferation T-Lymphocyte TRPV1 gene Testing Tumor Immunity Tumor-infiltrating immune cells Woman Work adaptive immune response adaptive immunity afferent nerve anti-PD-1 anti-tumor immune response antitumor effect cell growth chemotherapy cytotoxic draining lymph node human disease immune function improved inhibitor lymph flow malignant breast neoplasm migration neoplastic cell nerve supply neurotransmission novel pathogenic bacteria peptide P programmed cell death protein 1 receptor response secondary lymphoid organ therapeutic evaluation translational cancer research tumor tumor growth tumor microenvironment tumorigenesis

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。