01whole.pdf (2.24 MB)
Glycomic profiles of Interferon-gamma (IFN-γ) treated melanoma cells may indicate patient response to immunotherapy
thesisposted on 2022-03-29, 02:46 authored by Janine Sleiman
Immunotherapy has shown favourable results in prolonging survival of melanoma patients. Response to immunotherapy is partly dependent on interferon gamma (IFN-γ) a cytokine that mediates immune activity by inducing antigen presentation (i.e. HLA-ABC) and immune checkpoint molecules (i.e. programmed death ligand-1 and -2, PD-L1 and PD-L2). A recent study has shown that PD-L1 glycosylation promotes its stabilisation and immunosuppressive activity. Protein glycosylation regulates its structure, function and interaction. In this research project, we investigated the effects of IFN-γ treatment on the expression of immune activity molecules HLA-ABC, PD-L1 and PD-L2, and the level of cell surface glycosylation on 16 melanoma cell lines, using flow cytometry and liquid chromatography-mass spectrometry. We hypothesize that glycosylation profiles may influence response to immunotherapy. Our results indicated that IFN-γ induced expression of immune molecules PD-L2 and HLA-ABC on the majority of melanoma cells. This study also showed that glycosylation levels were not affected by IFN-γ treatment, however the levels of glycosylation differed between melanoma cell lines. Differences in the extent and type of glycosylation in each melanoma cell line may be associated with tumour progression and immunotherapy response.