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| ID | Type | Description | Link |
|---|---|---|---|
| 8230162487 | Other Grant/Funding Number | The National Natural Science Foundation of China |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| glioma patients receiving conventional treatment | surgery+radiotherapy+chemotherapy | ||
| glioma patients with tumor vaccine | surgery+radiotherapy+chemotherapy+tumor vaccine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tumor vaccine | Biological | DC vaccine produced by the Team |
|
| Measure | Description | Time Frame |
|---|---|---|
| IHC analysis | 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. | 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Transcriptomics | The issues collected will be used for transcriptome sequencing to measure gene expression level. | 36 months |
| Immunomics | The issues collected will be used for TCR/BCR sequencing to measure clonality of lymphocytes |
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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
Exclusion Criteria:
Patients who meet any of the following criteria will not be included in this study:
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Patients undergoing glioma surgery at Huashan Hospital
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Di Chen | Recruiting | Shanghai | Shanghai Municipality | 200040 | China |
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| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D019496 | Cancer Vaccines |
| ID | Term |
|---|---|
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| 36 months |
| Proteomics | The issues collected will be used for proteomic sequencing to measure gene expression level in protein | 36 months |
| Radiomics | The features from images will be extracted using algorithm of Deep-learning or Radiomics | 36 months |
| Genomics | The issues collected will be used for whole genome sequencing or whole exome sequencing to measure gene mutations. | 36 months |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |