Developing Novel Therapeutic Approaches Targeting Macrophages in GBM

开发针对 GBM 巨噬细胞的新型治疗方法

基本信息

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
项目类别：
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

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

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项目摘要

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.

项目摘要 GBM仍然是最致命的脑癌，没有有效的疗法。已经表明 GBM中的大多数基质细胞是肿瘤相关的巨噬细胞（TAM），有助于肿瘤微环境异质性并促进GBM进展。我们最近有定义的分子途径导致巨噬细胞募集和极化。我们的初步数据表明，GBM中的PTEN突变/缺失通过增强来触发免疫反应通过LOX募集巨噬细胞。此外，我们还将TBK1确定为钥匙信号传导节点调节巨噬细胞极化。目标1：我们将阐明 LOX介导的GBM中的巨噬细胞募集；目标2：我们将确定的分子基础 TBK1介导的GBM中的巨噬细胞极化；目标3：我们将执行临床前试验的目标 LOX和TBK1与护理标准和免疫检查点结合使用以发展 GBM患者的新型治疗方法。