The Role of B7-H4 in Tumor Vaccine
Recruiting now
Conditions studied: Glioma
In brief
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.
Key facts
- Study ID
- NCT06156150
- Run by
- Huashan Hospital
- People needed
- 160
- Starts
- 2023-11-26
- Expected to finish
- 2026-12-31
- Last updated by the study team
- 2023-12-05
Who can join
Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- 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.
You may not qualify if…
- Patients who meet any of the following criteria will not be included in this study:
- Participants in other clinical trials;
- Pregnant women.
Where it is running
- Di Chen — Shanghai, Shanghai Municipality, China (enrolling)
Full record on ClinicalTrials.gov
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