权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Contribution of myeloid cells to the anti-tumor adaptive immune response after radiation in a pediatric brain tumor

骨髓细胞对小儿脑肿瘤放疗后抗肿瘤适应性免疫反应的贡献

基本信息

批准号：
10664681
负责人：
MAI T DANG
金额：
$ 23.81万
依托单位：
WASHINGTON UNIVERSITY
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：
2023-05-01 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10664681
关键词：
Ablation Adult Affect Antigen Presentation Antigen-Presenting Cells Antigens Area Biological Assay Brain Brain Glioblastoma Brain Neoplasms CD8-Positive T-Lymphocytes Cause of Death Cell Survival Cell physiology Cells Cellular Immunity Child Childhood Childhood Brain Neoplasm Childhood Malignant Brain Tumor Clinical Coupled Cytotoxic T-Lymphocytes Data Dendritic Cells Development Disease remission Fellowship Functional disorder Genetic Genetic Transcription Genetically Engineered Mouse Goals Head Heterogeneity Immune Immune response Immune system Immunity Immunology Immunosuppression Immunotherapy Impairment Infiltration Institution Intervention Investigation Knowledge Laboratories Macrophage Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Measures Mediating Mentors Mentorship Microglia Morbidity - disease rate Mus Myeloid Cells Myeloid-derived suppressor cells Natural Immunity Neurology Neurosciences Neutrophil Infiltration Non-Small-Cell Lung Carcinoma Oncology Operative Surgical Procedures Patients Pediatric Hospitals Pediatric Neurology Pharmaceutical Preparations Phenotype Philadelphia Physicians Play Population Positioning Attribute Radiation Radiation therapy Recurrence Regulation Research Resistance Role Scientist Seasons Site T cell response T-Cell Activation T-Cell Proliferation T-Lymphocyte Testing Therapeutic Intervention Training Training Programs Treatment Efficacy Tumor Immunity Universities Washington Work adaptive immune response adaptive immunity anti-tumor immune response antitumor effect arm cancer stem cell career cell killing chemotherapy clinical training cytotoxic draining lymph node immune checkpoint blockade improved improved outcome medulloblastoma melanoma monocyte neoplastic cell nervous system disorder neuro-oncology neutrophil new therapeutic target novel novel therapeutics pediatric patients professor radiation effect recruit response side effect single cell analysis skill acquisition tenure track tool transcriptomics treatment response treatment strategy tumor tumor immunology tumor microenvironment tumor-immune system interactions

项目摘要

Project Summary The goal of the proposed 5-year training program is to facilitate Dr. Mai Dang’s full transition to an independent physician scientist. Her work is focused on identifying novel ways to modulate the brain tumor immune microenvironment to improve treatment strategies for pediatric patients. Dr. Dang’s research background is in neuroscience and her clinical training in pediatric neurology, which was completed at the Children’s Hospital of Philadelphia. After clinical fellowship, she received additional clinical training in neuro- oncology while completing her fellowship research on identifying the heterogeneity of myeloid cells in medulloblastoma. She was recently recruited to Washington University in St. Louis as a tenured-track assistant professor in the Department of Neurology to continue this work with strong institutional support. She will use the next five years of mentored training to acquire additional essential knowledge on immunology and advanced research tools to perform investigations in cancer immunology. While her prior work was specifically on macrophages and microglia, her current proposal will focus on antigen presenting cells and their interaction with the adaptive arm of the immune system. Dr. Dang will be mentored by Dr. Milan Chheda, a physician scientist, whose expertise is on developing new therapies that target glioblastoma brain tumor cancer stem cells and the tumor microenvironment. She will be co-mentored by Dr. David DeNardo, who has expertise in immunology and the tumor microenvironment’s regulation of therapy response in pancreatic and lung cancer. They will be joined by a committee comprised of two highly seasoned mentors, both physician scientists with excellent track record for and commitment to training other physician scientists at WUSTL. Dr. Christine Gurnett is Head of Pediatric neurology, who is highly recognized for her work in the genetics of neurological disorders, and Dr. Joshua Rubin, Professor in Oncology is an expert on pediatric and adult brain tumors. This team is deeply committed to providing Dr. Dang with scientific, technical, and career mentorship to assist her in this launch of her independent research career. The research goal of this proposal is to identify reversible causes of immune suppression in medulloblastomas treated with radiation. The central hypothesis is that effective tumor immunity after radiation in a pediatric brain tumor will require both reducing suppressive myeloid cells and increasing functional antigen presenting cells. She will use advanced tools such as inducible depletion of immune cells and single-cell analysis paired with assays to directly measure the function of antigen presenting cells and cytotoxic T cells to study this hypothesis. Findings from this work will uncover ways to effectively use immunotherapy to augment radiation efficacy to improve overall survival and morbidity for pediatric brain tumor patients.

项目总结