Immune regulatory metabolites in the tumor microenvironment suppress T cell function in ovarian cancer
| dc.contributor.author | Kilgour, Marisa | |
| dc.contributor.supervisor | Lum, Julian J. | |
| dc.date.accessioned | 2022-04-27T00:16:39Z | |
| dc.date.copyright | 2022 | en_US |
| dc.date.issued | 2022-04-26 | |
| dc.degree.department | Department of Biochemistry and Microbiology | |
| dc.degree.level | Doctor of Philosophy Ph.D. | en_US |
| dc.description.abstract | Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a striking enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared to ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer. | en_US |
| dc.description.embargo | 2023-04-13 | |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/13879 | |
| dc.language | English | eng |
| dc.language.iso | en | en_US |
| dc.rights | Available to the World Wide Web | en_US |
| dc.subject | Cancer | en_US |
| dc.subject | Immunology | en_US |
| dc.subject | Metabolism | en_US |
| dc.title | Immune regulatory metabolites in the tumor microenvironment suppress T cell function in ovarian cancer | en_US |
| dc.type | Thesis | en_US |