Interrogating Mechanisms of Anti-tumor Immunity in Human Subjects and Murine Models of IDH-Mutant Glioma Treated with All-Trans Retinoic Acid and PD-1 Inhibition

探讨全反式视黄酸和 PD-1 抑制治疗的人类受试者和 IDH 突变神经胶质瘤小鼠模型的抗肿瘤免疫机制

• 批准号: 10739154
• 负责人: Nduka Mgbechinyere Amankulor
• 金额: $ 68.31万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-03 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739154
• 关键词: Address; Adjuvant; Age; Antibodies; Biological Markers; Blood; Brain; Brain Neoplasms; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; CD8B1 gene; Cells; Cessation of life; Chemotherapy and/or radiation; Clinical; Clinical Trials; Combined Modality Therapy; Data; Development; Diffuse; Disease remission; Dose; Epigenetic Process; Evaluation; Excision; Exclusion; Exhibits; Future; Gene Expression Profile; Genetic Transcription; Genotype; Glioma; Goals; Hematologic Neoplasms; Human; Immune; Immune checkpoint inhibitor; Immune system; Immunocompetent; Immunologic Markers; Immunologic Monitoring; Immunologic Surveillance; Immunologics; Immunosuppression; Immunotherapeutic agent; Immunotherapy; Infiltration; Inflammatory; Institutional Review Boards; Interferon Type II; Interferons; Isocitrate Dehydrogenase; Knowledge; Lymphocyte; Lymphocyte Function; Lymphocytic Infiltrate; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of brain; Mediating; Mediator; Modality; Modeling; Mus; Mutation; Myelogenous; Myeloid-derived suppressor cells; Natural Killer Cells; Neoadjuvant Therapy; Operative Surgical Procedures; Output; PD-1 inhibitors; Pathway interactions; Patients; Pennsylvania; Performance; Phase II Clinical Trials; Population; Prediction of Response to Therapy; Recurrence; Regimen; Regulatory T-Lymphocyte; Reporting; Resistance; Retinoids; Sampling; Series; Signal Pathway; Signal Transduction; Sleeping Beauty; Solid; Specificity; Specimen; T cell receptor repertoire sequencing; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte and Natural Killer Cell; Techniques; Testing; Therapeutic; Therapeutically Targetable; Tissues; Tretinoin; Tumor Biology; Tumor Immunity; Tumor Tissue; Tumor-Infiltrating Lymphocytes; Universities; Validation; XCL1 gene; cell type; checkpoint inhibition; clinical efficacy; cohort; design; epigenetic silencing; exhaustion; experimental study; gene network; genetic signature; human subject; immune checkpoint blockade; immunogenic; immunogenicity; mouse model; mutant; neoplastic cell; pre-clinical; predicting response; programmed cell death protein 1; response; restoration; small molecule; specific biomarkers; transcriptome sequencing; treatment response; tumor; tumor eradication; young adult

Project Abstract Diffuse gliomas are fatal brain tumors that respond poorly to current immunotherapies. Using both mice models and human clinical trial data, we propose a series of experiments to identify immune biomarkers and key immune cell types that predict tumor responsiveness to therapy. These results will further our understanding of brain tumor biology and inform the future development of new treatment modalities.

项目摘要 弥漫性神经胶质瘤是致命的脑肿瘤，对当前的免疫疗法反应不佳。使用 无论是小鼠模型还是人体临床试验数据，我们提出了一系列实验来确定 预测肿瘤对治疗反应的免疫生物标志物和关键免疫细胞类型。 这些结果将进一步加深我们对脑肿瘤生物学的理解并为未来提供信息 开发新的治疗方式。