Characteristics of Human Cytomegalovirus specific T-Cells in Glioblastoma Multiforme

Alexander, Hamish Stewart (2015). Characteristics of Human Cytomegalovirus specific T-Cells in Glioblastoma Multiforme MPhil Thesis, School of Medicine, The University of Queensland. doi:10.14264/uql.2015.735

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Author Alexander, Hamish Stewart
Thesis Title Characteristics of Human Cytomegalovirus specific T-Cells in Glioblastoma Multiforme
School, Centre or Institute School of Medicine
Institution The University of Queensland
DOI 10.14264/uql.2015.735
Publication date 2015-06-26
Thesis type MPhil Thesis
Supervisor David Walker
Rajiv Khanna
Total pages 100
Language eng
Subjects 110709 Tumour Immunology
111204 Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
Formatted abstract
Glioblastoma Multiforme (GBM) is the most common primary brain malignancy and invariably fatal. Evidence has emerged showing human cytomegalovirus (HCMV) infection is present in GBM, providing a possible target for new immunotherapeutic agents. This thesis aims to examine the functional characteristics of T-cell responses to GBM, including HCMVspecific T-Cells. To examine the effects of exposure HCMV in patients with GBM an 80 patient cohort was assessed. No difference was seen between HCMV seropostive and seronegative patients with median progression free survival of 344 days vs. 348 days (p=0.453) and median overall survival s 719 days vs. 780 days (p=0.553). To further investigate HCMV immunity in GBM, gene microarray analysis was performed on CD8+ Tcells and HCMV specific T-cells from GBM patients. Analysis of CD8+ T-cells in GBM patients showed down regulation of genes in two distinct subgroups related to effector function and the exhausted phenotype of T-cells usually seen in persistent virus infection. Included in this was significant up regulation of the co-inhibitory gene BTLA along with down regulation of the gene for co-stimulatory molecule LIGHT. These are both ligands of Herpes Virus Entry Mediator (HVEM) suggesting this may be an important pathway of immune suppression in GBM. Flow Cytometry studies however failed to confirm differences in surface expression of these molecules in T-cells of GBM patients. HVEM was however seen to be expressed in tissue in a significant number of tumours examined by immunohistochemistry. Further studies are required to define the role of these pathways and their suitability for manipulation as a standalone therapy or adjunct to other immunotherapeutic strategies.
Keyword Glioblastma multiforme
Human Cytomegalovirus
Cytotoxic T Cells
Inhibitory Receptor
Immune response
Gene expression analysis

Document type: Thesis
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Created: Wed, 03 Jun 2015, 23:05:23 EST by Hamish Stewart Alexander on behalf of Examinations