Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 20 for “"T Cell Exhaustion"”.
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T Cell Exhaustion in Glioblastoma
… of immunotherapy which seeks to perpetuate T cell activity by blocking inhibitory immune checkpoints. This strategy has gained FDA approval in several solid tumors, yet has failed in GBM. Severe T cell dysfunction such as T cell exhaustion is a known contributor to failures of immune …
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The Role of TCR Engagement Strength in Antitumor CD8 T Cell Exhaustion
… by the persistence of progenitor exhausted CD8 T cells (Tpex). Tpex serve as a source for the pool of effector T cells that tend to have a short lifespan or eventually become dysfunctional in uncleared tumors. In contrast to the short-lived feature of their daughter cells, Tpex are able to …
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A novel antigen-receptor signalling reporter mouse reveals clonotype-independent intratumoral trapping as a spatial feature of CD8+ T cell exhaustion
… labelled. Combining isolation of the EYFP+ cells with further technologies would enable in-depth analysis of their cell states, clonotype, tissue location, and labelling localization. Validating the AgRSR model, I first showed that the system is robust in its dependencies for TCR signalling …
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Investigating CD8+ T-cell gene expression signatures as disease prognostic biomarkers in paediatric inflammatory bowel disease.
… of gene expression profiles from CD8+ T-cells in adult IBD cohorts identified promising signatures, including a T-cell exhaustion signature, to predict disease outcome in these patients. Hypothesis and aim: We hypothesised that adult CD8+ T-cell prognostic signature and T-cell exhaustion …
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TOX2 and TOX at the intersection of central memory and exhaustion in human CAR T cells
… treating solid tumors has been limited due to T cell exhaustion, which limits their proliferation and cytotoxicity when chronically stimulated with antigen, such as in cancer. Genetic modification of CAR T cells is one approach to improve tumor killing capacity. We profiled a patient with chronic …
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Mathematical Models of Underlying Dynamics in Acute and Chronic Immunology
… that there are key differences between the cells and cytokines that are present in a primary response versus those present in subsequent responses. Specifically, after a primary response, memory cells are present and drive the clearance of antigen in these later immune responses. When …
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Sex-influenced histopathological changes and the immunity during Toxoplasma gondii infection
… genes associated with PI3K/AKT/mTOR pathway, T cell exhaustion and apoptosis/pyroptosis. Consistent with these observations, female mice developed greater levels of DNA fragmentation as determined by TUNNEL and increased expression of NLRP3 in their brains. Overall, the results suggest that …
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Continuous expression of TOX safeguards exhausted CD8 T cell epigenetic fate
CD8 T cell exhaustion is a major barrier limiting anti-tumor therapy. Though checkpoint blockade temporarily improves exhausted CD8 T cell (Tex) function, the underlying epigenetic landscape of Tex remains largely unchanged, preventing their durable “reinvigoration.” Whereas the transcription …
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A study of immune responses during antiviral treatment for hepatitis C virus infection
… with risk of developing liver failure and hepatocellular carcinoma (HCC). As a consequence, HCV is the most common indication for liver transplantation in developed countries. Chronic hepatitis C infection is characterised by a failure of HCV specific T cell responses caused by viral escape and T …
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Regulation of Anti-Viral Cd8+ T Cell Responses by the Pd-1 Pathway
… immunoregulatory pathway for modulating CD8+ T cell responses. This pathway has become an important therapeutic target in cancer and chronic viral infections, where blockade of PD-1/PD-L1 reverses CD8+ T cell exhaustion and improves outcomes. However, it remains unclear how PD-1 pathway signals …
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CD4+ T cells in the pathogenesis of visceral leishmaniasis
… leishmaniasis, caused by infection with the intracellular protozoan Leishmania donovani, is a chronic disease that affects the spleen, liver and bone marrow. Patients present with high parasite burdens in visceral organs, splenomegaly, cachexia, pancytopenia and will progress to death if not …
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The role of tissue-resident immune cells in PanIN to PDAC progression
… Tissue-resident group 2 innate lymphoid cells (ILC2) are emerging as important immune modulators of the cancer microenvironment, although their role in PDAC remains contentious with both pro- and anti-cancer roles having been described. In this thesis, I have characterised the role of …
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POST-EXPOSURE TREATMENT OF MARBURG VIRUS ANGOLA DISEASE IN NON-HUMAN PRIMATES USING RECOMBINANT VESICULAR STOMATITIS VIRUS VECTORS
… that succumbed had T helper 2 and regulatory T cell signatures; upregulation of genes associated with T-cell exhaustion; and delayed interferon signaling. Only survivor macaques formed MARV GP-specific IgM and IgG with low levels of neutralizing antibodies, and these animals had more …
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Not-so-innocent bystanders? Investigating non-antigen specific CD8+ T cell activation in autoimmune prognosis
… a novel gene expression signature in T cells predictive of clinical outcome in anti-neutrophil cytoplasmic antibodies-associated vasculitis, systemic lupus erythematosus, Crohn’s disease, and ulcerative colitis that is not associated with diagnosis. Two modules (corresponding to sets of …
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T cell phenotyping of a mouse model of Activated PI3Kdelta syndrome
… and herpes group virus infections. Following T cell receptor (TCR) stimulation, T cells from these patients undergo increased activation induced cell death, which can be reversed by selective PI3Kdelta inhibitors. I used a new conditional knock-in mouse (T-p110delta E1020K) in order to …
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Single Cell Analysis of the HIV-1 Latent Reservoir
… of rare, long-lived, latently infected cells. These cells, called the latent reservoir, are thought to resist immune clearance and viral cytopathic effects by harboring a transcriptionally quiescent integrated HIV-1 provirus. As a result, interruption of suppressive therapy almost …
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Tumour infiltrating T cells in non-small cell lung cancer and their interactions with cancer-associated fibroblasts
… is aimed at reinvigorating local cytotoxic T cells, however the rate of immunotherapy failure in non-small cell lung cancer (NSCLC) is as high as 80%. An improved mechanistic understanding of immunosuppressive pathways in NSCLC is important to develop novel diagnostic and therapeutic …
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Evolution of adaptive immune response from acute to chronic phase of hepatitis C virus infection
The CD8+ T cell responses play a pivotal role in controlling viral replication during HCV infection. HCV evades the immune system by rapid viral evolution affording escape from immune selection pressure including at MHC-I restricted epitopes. However, some CTL epitopes remain conserved well past …
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Differential progression of pancreatic premalignancy in geographically distant murine transgenic cohorts uncovers key role of microbial metabolites
… Expression of these mutations in select cellular compartments has resulted in the ability to recapitulate characteristics of human pancreatic cancer such as the development of precursor lesions, metastatic activity, and cytokine signaling. These models represent convenient and …
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Characterizing T Cell Features of Atypical Lymphocytes for the Optimization of Adoptive Immunotherapies
… results. Two such populations are regulatory T cells (Tregs) and CAR (chimeric antigen receptor-modified) T cells. The functional role of Tregs in the immune system is non-canonical, in that they prevent hyper-inflammation and resolve immunopathology by constraining conventional immune cell …