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| Status |
Public on Jun 03, 2024 |
| Title |
Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution (bulk RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of NY-ESO-1 in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres, we demonstrate in vitro that basal NY-ESO-1 expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing and renders NY-ESO-1 an inducible tumor antigen. Targeting of DAC-induced NY-ESO-1 in primary GBM cells promotes specific and polyfunctional NY-ESO-1 TCR-T cell responses. DAC further upregulates other tumor-associated cancer testis antigens concomitantly with tumor-intrinsic reactivation of human endogenous retroviruses (hERV) and type I interferon. Overall, we demonstrate that DAC promotes an inducible tumor antigen and enhances T cell functionality against GBM.
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| |
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| Overall design |
To characterize the effects of Decitabine on primary and immortalized glioma cell lines.
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| |
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| Contributor(s) |
Lai TJ, Sun L, Prins TJ, Treger J, Li T, Sun MZ, Nathanson DA, Liau LM, Lai A, Prins RM, Everson RG |
| Citation(s) |
38856710 |
| |
| Submission date |
Mar 08, 2024 |
| Last update date |
Aug 16, 2024 |
| Contact name |
Thomas Jasper Lai |
| E-mail(s) |
[email protected]
|
| Phone |
7472286309
|
| Organization name |
University of California; Los Angeles
|
| Department |
Neurosurgery
|
| Lab |
Prins
|
| Street address |
Gonda Room 1554 695 Charles E. Young Dr.
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL34284 |
Illumina NovaSeq X Plus (Homo sapiens) |
|
| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE261191 |
Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution |
|
| Relations |
| BioProject |
PRJNA1085732 |
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