Thesis
The effects of IFNγ, TNFα, and Dexamethasone onthe Immunopeptidome of Diffuse Intrinsic PontineGlioma
Diffuse Intrinsic Pontine Glioma (DIPG) is a malignant tumor found in the brain stem which mainly
affects children. It has an aggressive nature with no available curative treatment. Cancer
immunotherapy using specific tumor antigens to target tumor cells may be a viable alternative
therapeutic option for DIPG, however antigen presentation is highly downregulated in tumors. This
study aims to achieve further understanding of the impacts of key pro-inflammatory cytokines towards
antigen presentation. In addition, this study would like to elucidate the effects of the
immunosuppressive drug dexamethasone. Two patient-derived DIPG cell lines, SU-DIPG-24 and SU-
DIPG-27, were treated with interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and
dexamethasone. Subsequently, the HLA class I and class II presentation levels of cells were analyzed
using flow cytometry. Results indicate that IFNγ induced an upregulation in HLA class I and class II
expression in both cell lines, while TNFα had limited effects on HLA expression in both cell lines, and
dexamethasone did not significantly affect HLA presentation levels. Overall, this study showed that
IFNγ is an ideal component to enhance HLA peptide presentation in tumor cells as a potential adjuvant
for enhancing the success chance of immunotherapy.
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