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Targeting myeloid cells to increase efficacy of immunotherapy against brain tumors.

靶向骨髓细胞以提高针对脑肿瘤的免疫疗法的功效。

基本信息

批准号：
10571040
负责人：
Tyler Eugene Miller
金额：
$ 21.15万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
2023-07-19 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10571040
关键词：
Academia Address Advisory Committees Biological Models Biology Biotechnology Brain Brain Neoplasms Bromodomain CAR T cell therapy Cancer Patient Cells Clinical Communication Cues Cytotoxic T-Lymphocytes Data Development Plans EP300 gene Effectiveness Effector Cell Epigenetic Process Faculty Gene Silencing General Hospitals Genomics Glioblastoma Grant Immune Immune checkpoint inhibitor Immune system Immunology Immunology procedure Immunosuppression Immunotherapy Invaded Laboratories Leadership Life Macrophage Malignant Neoplasms Malignant neoplasm of brain Massachusetts Mentors Mentorship Methods Microglia Mitochondria Modeling Mutation Detection Myelogenous Myeloid Cells Myeloid-derived suppressor cells Organoids Pathology Patients Peripheral Phenotype Physicians Positioning Attribute Primary Neoplasm Professional Competence Program Development Recording of previous events Recurrence Refractory Research Research Proposals Running Sampling Scientist Structure System T cell infiltration Technical Expertise Techniques Therapeutic Training Work Writing cDNA Library cancer type career development cell transformation design experience experimental study genomic data inhibitor migration monocyte mutant neoplastic cell peripheral blood prevent programs rational design single-cell RNA sequencing skills small molecule small molecule inhibitor targeted treatment therapeutic target therapy design tool transcription factor transcriptome tumor tumor microenvironment

项目摘要

PROJECT SUMMARY The proposed research career development program seeks to investigate the mechanism by which myeloid cells in brain tumors become immunosuppressive, preventing the immune system from controlling the tumor even in the presence of immunotherapy designed to activate it. The candidate is currently a Research Fellow 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 immune biology and advanced immune assay techniques. The structured career development plan includes training and mentorship in laboratory management, scientific leadership, research communications, grant writing, and other critical career skills. These technical and career skills will be acquired under the guidance of Dr. Bradley Bernstein, who will serve as primary mentor and has a history of trainees that obtain group leader positions in academia, as well as a Research Advisory Committee of word-class scientists including Drs. Mario Suva, John Iafrate, and Nir Hacohen. Through this comprehensive program, the candidate will acquire a unique set of clinical and 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 brain cancer epigenetics and immunology. The research strategy will investigate immunosuppressive tumor-associated myeloid cells in brain tumors – where they come from, the epigenetic mechanism by which they become immunosuppressive, and how to potentially transform them. Transforming or selectively killing myeloid cells that express immunosuppressive programs offers great opportunity to sensitize brain tumors to immunotherapy. However, it remains unknown if these myeloid cells come from circulating monocytes or endogenous microglia, or what make them immunosuppressive, significantly hindering the design of rational clinical strategies to target these cells in brain tumors. The aims of this proposal are to: (1) Determine the origin of immunosuppressive myeloid cell states in brain tumors, (2) identify the epigenetic regulatory factors that maintain the immunosuppressive cell program, (3) discover perturbations that eliminate or transform immunosuppressive myeloid cells. Overall, these studies will provide valuable data needed to develop targeted therapies against immunosuppressive myeloid cells and increase the efficacy of immunotherapy for brain cancer patients.

项目总结