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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 04, 2024 |
| Title |
Epigenetic priming induces cancer testis antigens and human endogenous retroviruses in glioma for enhanced T cell responses at single cell resolution (methylation) |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| 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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| Overall design |
To characterize the effects of Decitabine on primary and immortalized glioma cell lines.
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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 |
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| Submission date |
Mar 08, 2024 |
| Last update date |
Aug 16, 2024 |
| Contact name |
Thomas Jasper Lai |
| E-mail(s) |
THOMASJLAI@GMAIL.COM
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| Phone |
7472286309
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| Organization name |
University of California; Los Angeles
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| Department |
Neurosurgery
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| Lab |
Prins
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| Street address |
Gonda Room 1554 695 Charles E. Young Dr.
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL23976 |
Illumina Infinium HumanMethylation850 BeadChip |
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| Samples (20)
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| GSM8137117 |
genomic DNA, GS025, DMSO, 1 |
| GSM8137118 |
genomic DNA, GS081, DAC, 1 |
| GSM8137119 |
genomic DNA, GS081, DMSO, 1 |
| GSM8137120 |
genomic DNA, GS243, DAC, 2 |
| GSM8137121 |
genomic DNA, GS243, DAC, 1 |
| GSM8137122 |
genomic DNA, GS243, DMSO, 2 |
| GSM8137123 |
genomic DNA, GS243, DMSO, 1 |
| GSM8137124 |
genomic DNA, GS277, DAC, 1 |
| GSM8137125 |
genomic DNA, GS277, DMSO, 1 |
| GSM8137126 |
genomic DNA, GS351, DAC, 1 |
| GSM8137127 |
genomic DNA, GS351, DMSO, 1 |
| GSM8137128 |
genomic DNA, U251, DAC, 2d, 1 |
| GSM8137129 |
genomic DNA, U251, DAC, 4d, 3 |
| GSM8137130 |
genomic DNA, U251, DAC, 4d, 2 |
| GSM8137131 |
genomic DNA, U251, DAC, 4d, 1 |
| GSM8137132 |
genomic DNA, U251, DMSO, 2 |
| GSM8137133 |
genomic DNA, U251, DMSO, 1 |
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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 |
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| Relations |
| BioProject |
PRJNA1085733 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261190_RAW.tar |
280.9 Mb |
(http)(custom) |
TAR (of IDAT) |
| Raw data provided as supplementary file |
| Processed data included within Sample table |
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