Glioma
Conditions
Keywords
glioma, treatment resistance, immunotherapy, cancer vaccine, macrophage
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.
Interventions
BIOLOGICALtumor vaccine
DC vaccine produced by the Team
Sponsors
Huashan Hospital
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IHC analysis | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transcriptomics | 36 months | The issues collected will be used for transcriptome sequencing to measure gene expression level. |
| Immunomics | 36 months | The issues collected will be used for TCR/BCR sequencing to measure clonality of lymphocytes |
| Proteomics | 36 months | The issues collected will be used for proteomic sequencing to measure gene expression level in protein |
| Radiomics | 36 months | The features from images will be extracted using algorithm of Deep-learning or Radiomics |
| Genomics | 36 months | The issues collected will be used for whole genome sequencing or whole exome sequencing to measure gene mutations. |
Countries
China
Outcome results
None listed