Developing Novel Therapeutic Approaches Targeting Macrophages in GBM

开发针对 GBM 巨噬细胞的新型治疗方法

• 批准号: 10380595
• 负责人: Y. Alan Wang
• 金额: $ 0.34万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380595
• 关键词: Adult; Antibodies; Behavior; Bone Marrow; Cells; Chemotactic Factors; Clinical; Combined Modality Therapy; Cytometry; Data; Deletion Mutation; Development; Diagnosis; Exhibits; Gene set enrichment analysis; Genetic; Genomics; Glioblastoma; Heterogeneity; Immune; Immune response; In Vitro; Infiltration; Knockout Mice; Knowledge; Malignant neoplasm of brain; Mediating; Modeling; Molecular; Mus; PTEN gene; PTK2B gene; Pathway interactions; Patients; Phenotype; Process; Protein-Lysine 6-Oxidase; Proteomics; Proto-Oncogene Proteins c-akt; Radiation therapy; Role; Sampling; Signal Pathway; Signal Transduction; Specimen; Stromal Cells; Subgroup; System; TANK-binding kinase 1; Therapeutic; Therapeutic Trials; Tumor-associated macrophages; Up-Regulation; Validation; bone; cancer cell; chemoradiation; chemotherapy; cytokine; effective therapy; immune checkpoint blockade; immunosuppressive macrophages; in vivo; inhibitor; loss of function; macrophage; migration; monocyte; mouse model; neutralizing antibody; new therapeutic target; novel; novel therapeutic intervention; osteopontin; pre-clinical; preclinical trial; recruit; standard of care; therapeutic target; therapeutically effective; transcriptome; transcriptome sequencing; transcriptomics; translational potential; translational study; tumor; tumor microenvironment

Project Summary GBM remains the most lethal brain cancer with no effective therapeutics. It has been shown that the majority of stromal cells in GBM are tumor-associated macrophages (TAMs), which contribute to tumor microenvironment heterogeneity and promote GBM progression. We have recently defined molecular pathways leading to macrophage recruitment and polarization. Our preliminary data showed that PTEN mutation/deletion in GBM triggers immune response by enhancing macrophage recruitment through LOX. In addition, we have also identified TBK1 as a key signaling node regulating macrophage polarization. Aim 1: we will elucidate the mechanism of LOX mediated macrophage recruitment in GBM; Aim 2: we will determine the molecular basis of TBK1 mediated macrophage polarization in GBM; Aim 3: we will perform preclinical trials targeting LOX and TBK1 in combination with standard of care and immune checkpoint blockade to develop novel therapeutic approach for GBM patients.

项目总结