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| Status |
Public on May 16, 2024 |
| Title |
TET2 Promotes Tumor Antigen Presentation and T Cell-Directed Tumor Cell Cytotoxicity Which is Enhanced by Vitamin C Treatment |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune evasion by tumors is promoted by low T cell infiltration, an immunosuppressive tumor microenvironment, poor T cell activity directed against the tumor, and reduced tumor antigen presentation. We showed previously that tumor expression of the DNA dioxygenase TET2 enhances recruitment of T cells through activating the expression of CXCL9, 10 and 11. Vitamin C treatment was shown to increase these effects in a TET2 dependent manner. Using scSeq analysis, we show that an additional function for TET2 in tumors is to enhance the expression of genes involved in antigen presentation, including those encoding H-2 MHC proteins, B2M, TAP1, TAPBP, and components of immunoproteasome. Using the B16-OVA melanoma model, we show that antigen expression in tumors is blocked if TET2 expression is eliminated and that vitamin C further promotes tumor antigen presentation in a TET2-dependent manner. Consistently, T cell killing assays demonstrate that effective killing of tumor by antigen-specific T cells requires TET2 expression in the tumor cells. Analysis of patient tumor samples indicates that TET2 activity, as measured through 5hmC levels, correlates directly with expression of antigen-presentation gene expression and with patient outcomes.
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| Overall design |
WT or TET2-KO B16-OVA melanoma cells were transplanted to C57BL/6 syngeneic mice and then treated with PBS or 1g/kg Vitamin C (I.V.) for 2 weeks starting from Day 6. Tumor tissues were then collected and single cell population were isolated for single-cell RNA Seq using 10X Genomics NGS.
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| Contributor(s) |
Cheng M, Chu A, Welch J, Baldwin A |
| Citation missing |
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| Submission date |
Mar 22, 2023 |
| Last update date |
May 16, 2024 |
| Contact name |
Meng Cheng |
| E-mail(s) |
chengmeng930817@gmail.com
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| Phone |
9198690473
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| Organization name |
UNC-CH
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| Department |
Lineberger Cancer Center
|
| Lab |
The Baldwin Lab
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| Street address |
107 Pinegate Cir, Apt 9
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27514 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA947645 |
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