Clinical trial NCT06156150: The Role of B7-H4 in Tumor Vaccine
Official title: The Role and Mechanism of B7-H4/ATF3 Axis From Glioma Associated Macrophages in Treatment Resistance of Cancer Vaccine
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioma
Keywords: glioma
treatment resistance
immunotherapy
cancer vaccine
macrophage
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2023-12-05
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing glioma surgery at Huashan Hospital

Brief 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 criteria: 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.

Primary outcomes:
measure: IHC analysis
timeFrame: 36 months
Secondary outcomes:
measure: Transcriptomics
timeFrame: 36 months
measure: Immunomics
timeFrame: 36 months
measure: Proteomics
timeFrame: 36 months
measure: Radiomics
timeFrame: 36 months
measure: Genomics
timeFrame: 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Di Chen
state: Shanghai
Study officials:
References: