期刊
JOURNAL OF TRANSLATIONAL MEDICINE
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1479-5876-9-192
关键词
T cells; tumor immunity; decitabine; cancer testis antigens; Fas/Fas Ligand
资金
- NIH/NCI [K01 CA111402, R01 CA123396 ., R01 CA1122358]
- Jonsson Comprehensive Cancer Center
- Eli & Edyth Broad Center of Regenerative Medicine
- Stem Cell Research at UCLA
- Howard Temin NCI
- STOP Cancer Career Development award
Background: The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies. Methods: We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells. Results and Discussion: Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1-specific T cells. Conclusions: Such data supports the hypothesis that agents which alter epigenetic cellular processes may immunosensitize tumor cells to tumor-specific T cell-mediated lysis.
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