Faculty AdvisorKenneth L. Rock, M.D.
UMass Chan AffiliationsPathology
Document TypeDoctoral Dissertation
MetadataShow full item record
AbstractThe major histocompatibility complex class I (MHC-I) antigen presentation pathway is necessary for the immune system to be able to detect, control, and eliminate cancers. MHC-I binds oligopeptides derived from cellular proteins and presents them on the cell surface to CD8+ T cells. Consequently, the CD8+ T cells can monitor whether any cells are making abnormal proteins and, if so, can destroy those cells. Because MHC-I presentation is not essential for cell viability, immune selection pressure often leads to cancers that are MHC-I low as they can better evade CD8+ T cell recognition. It is, therefore, important to fully understand the mechanisms of MHC-I presentation as this will identify new ways to target and exploit the pathway for cancer therapeutics. Although several components of the MHC-I pathway have already been characterized, some knowledge gaps remain. Unbiased forward genetic screens from our lab identified some novel gene candidates, such as IRF2, which positively regulate MHC-I presentation. In this dissertation, I will reveal which antigen presentation pathway genes are transcriptionally controlled by IRF2 and contribute to the MHC-I presentation deficiency observed in cells lacking IRF2 and I will also show that IRF2 negatively regulates PD-L1 expression. By influencing both MHC-I antigen presentation and PD-L1 expression in this manner, cancers lacking IRF2 (of which there are many) are both harder to see and more difficult to eliminate.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/31236
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