Investigating the Dynamics of T cell Exhaustion in Glioblastoma and Other Solid Tumors
dc.contributor.advisor | Fecci, Peter | |
dc.contributor.author | Waibl Polania, Jessica | |
dc.date.accessioned | 2024-06-06T13:44:11Z | |
dc.date.available | 2024-06-06T13:44:11Z | |
dc.date.issued | 2024 | |
dc.department | Pathology | |
dc.description.abstract | While terminally exhausted T cells (Tex_term) retain important anti-tumor cytotoxic function, it is the relative preservation of renewable, stem-like progenitor exhaustion (Tex_prog) that better indicates immunotherapeutic responsivity. Therefore, elucidating the requirements for progression from Tex_prog to Tex_term takes on clinical significance, where the cellular interactions in a tumor microenvironment (TME) governing such progression remain poorly established. Employing glioblastoma (GBM) and other solid tumors as models of severe exhaustion, we provide a detailed characterization of the progression from Tex_prog to Tex_term within the TME, where we observe a striking and disproportionate loss of Tex_prog over time. We find exhaustion concentrated within tumor-specific T cell subsets, with cognate antigenic exposure requisite for acquisition of the Tex_term phenotype. However, we identify tumor-associated macrophages (TAM), and not tumor cells, as the source of antigenic exposure governing the Tex_prog to Tex_term transition. Using cell – cell interaction analysis, we additionally highlight candidate receptor–ligand communications that may be specifically mediating the progression to Tex_term within the TME. | |
dc.identifier.uri | ||
dc.rights.uri | ||
dc.subject | Immunology | |
dc.subject | Molecular biology | |
dc.subject | Brain metastasis | |
dc.subject | Glioblastoma | |
dc.subject | T cell exhaustion | |
dc.subject | Tumor associated macrophage | |
dc.subject | Tumor microenvironment | |
dc.title | Investigating the Dynamics of T cell Exhaustion in Glioblastoma and Other Solid Tumors | |
dc.type | Dissertation |
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