The Role of B7-H4 in Tumor Vaccine

Summary

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.

Eligibility

Inclusion Criteria:

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

1. They were 18-80 years old, male and female;
2. The pathological results of frozen section during operation were gliomas;
3. Tissue (6 mm \* 6 mm) can be used for cell sorting on the basis of not affecting clinical routine diagnosis;
4. Sign informed consent.

Exclusion Criteria:

Patients who meet any of the following criteria will not be included in this study:

1. Participants in other clinical trials;
2. Pregnant women.

Conditions2

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