The Role and Mechanism of B7-H4/ATF3 Axis From Glioma Associated Macrophages in Treatment Resistance of Cancer Vaccine
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- IHC analysis
研究概览
简要总结
Glioma patients have poor prognosis because of limited choices of treatment. Therapeutic cancer vaccines have been proved to improve survival in glioma, but resistance is a new challenge for vaccine treatment, and the mechanism is unclear. The applicant found in previous papers that glioma cells induced B7-H4 overexpression in macrophages, and the expression level of B7-H4 is highly correlated with vaccine resistance. Preliminary experiments indicated that B7-H4 protein in macrophages inhibited the expression of ATF3, STAT1 and CXCL9/10, which also resulted in decreased T cell infiltration in glioma model of mouse and was a negative factor of vaccine benefits. Therefore, the applicant hypothesize that B7-H4 inhibits STAT1 transcription by reducing expression of ATF3, resulting in decreased phosphorylated-STAT1 in nucleus, which inhibiting expression and secretion of chemokines 9/10. Thereby, reduced infiltration of T cells in microenvironment will be followed, which ultimately promotes resistance of vaccine treatment in glioma. The follow-up plan of this project will be conducted based on the cells, organoid platform and animal experiments to confirm the role and mechanism of macrophage-derived B7-H4 in secretion of chemokines for T cells and treatment resistance of vaccines. Moreover, the DC vaccine produced by team of the applicant will be used to assess the probability of reversing vaccine resistance when intervening B7-H4 axis. Finally, a model for evaluating clinical benefits from vaccine will be established based on data from clinical trials combining with expression of B7-H4 and clinicopathologic features. This study will provide new evidences for the treatment of cancer vaccines in gliomas.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •The patients with glioma in the Department of Neurosurgery of Huashan Hospital Affiliated to Fudan University who meet the following three conditions can be enrolled
- •They were 18-80 years old, male and female;
- •The pathological results of frozen section during operation were gliomas;
- •Tissue (6 mm * 6 mm) can be used for cell sorting on the basis of not affecting clinical routine diagnosis;
- •Sign informed consent.
排除标准
- •Patients who meet any of the following criteria will not be included in this study:
- •Participants in other clinical trials;
- •Pregnant women.
结局指标
主要结局
IHC analysis
时间窗: 36 months
Different expression level of proteins (CD3,CD8,B7-H4 et.ac) in Gliomas with different grades and molecular subgroups (100 cases) will be measured using immunohistochemical.
次要结局
- Radiomics(36 months)
- Transcriptomics(36 months)
- Immunomics(36 months)
- Proteomics(36 months)
- Genomics(36 months)