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Title	GILT expression alters tumorigenic molecules and HLA class II presentation in human melanoma cells
Author	Hathaway, Jessica D.
Date	2011
Affiliation/College	College of Graduate Studies
Department	Microbiology and Immunology
Extent	vi, 80 leaves : ill.; 29 cm
Source	QH 200 H363 2011
Subject.MeSH	Academic Dissertations--South Carolina Oxidoreductases Acting on Sulfur Group Donors Melanoma Immune System Phenomena
Collection	MUSC Theses and Dissertations
Contributing Institution	Waring Historical Library (MUSC)
Rights	Copyright is held by the author.
Language	English
Type	Text
Format	application/pdf
Media Type	Manuscripts
Resource Identifier	mtd2011_hathaway_jd
Abstract	Melanoma is the 6th most common cancer in the United States and accounts for 79% of skin cancer related deaths. While treatments such as surgery, radiation, and chemotherapy have been effective in dealing this disease in its early stages, these treatments often fail in treating late stage metastatic melanoma. Immunotherapies have been shown successful in treating a small percentage of patients with late stage melanoma, but these treatments do not provide a long-lasting CD8+ response to effectively clear the tumor. The majority of melanoma cells either express or can be induced to express HLA class II proteins. An optimum presentation of HLA class II proteins is essential for the activation of CD4+ T cells, which provide a sustained killing of malignant tumors by activating cytotoxic CD8+ T cells. Our laboratory has also shown that melanoma cells express very low to undetectable levels of Gamma-interferon Inducible Lysosomal Thiol-reductase (GILT). The absence of GILT perturbs HLA class II antigen processing and presentation in melanoma cells. Our recent data suggest that GILT expression may restore immune recognition of melanoma cells via HLA class II molecules. Here, melanoma cells were successfully transfected with GILT and tested for cytokine profiles, angiogenic and tumorigenic factors, and immune inhibitory molecules in these cells. Data suggests that GILT has an important role in the cytokine profile of melanoma cells. My study also suggests that GILT expression reduces angiogenic molecules such as IL-8 and VEG-F in melanoma cells. Mechanistic studies revealed that GILT insertion also reduced tumorigenic molecule paired box-3 protein (PAX-3) through the colocalization of these molecules. These data suggest that GILT expression plays multiple roles in altering melanoma pathology and immune recognition, which may help devise novel chemoimmunotherapeutics against metastatic melanoma. This study also suggests PAX-3 is susceptible to targeting, which could lead to a less metastatic phenotype of this disease.

GILT expression alters tumorigenic molecules and HLA class II presentation in human melanoma cells

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