Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA335704 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes
| PRJNA338813 | ENA
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (whole blood RNA-seq)
| PRJNA338797 | ENA
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (bulk RNA-seq of sorted CD8+ T-cells)
| PRJNA338796 | ENA
Project description:Teplizumab is approved for delay of diagnosis of type 1 diabetes and modulates new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and “partially exhausted” CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation.
2024-09-25 | GSE271063 | GEO
Project description:Teplizumab is approved for delay of diagnosis of type 1 diabetes and may modulate new onset disease. Compared to EBV seronegative patients, those who were EBV seropositive prior to treatment had a more robust response to drug in two clinical trials. We compared the phenotypes, transcriptomes, and development of peripheral blood cells before and after teplizumab treatment. Higher number of Tregs and partially exhausted CD8+ T cells were found in EBV seropositive individuals at the baseline in the TN10 and AbATE trials. Single cell transcriptomics and functional assays identified downregulation of NFkB and other pathways after treatment in treated EBV seropositive patients. Among diabetes antigen specific CD8+ T cells, T cell receptor and mTOR signaling were also reduced. Impairments in function of adaptive immune cells were enhanced by teplizumab treatment in EBV seropositive individuals. Our data indicate that EBV can impair signaling pathways in immune cells, that broadly redirect cell differentiation.
2025-05-15 | GSE296549 | GEO
Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (single-cell RNA-seq of sorted CD8+ T-cells)
| PRJNA338798 | ENA
Project description:Teplizumab, a humanized anti-CD3 monoclonal antibody, represents a major advancement in autoimmune type 1 diabetes (T1D) treatment, capable of delaying clinical onset in stage 2 and preserving beta cell function in early stage 3. However, therapeutic responses are heterogeneous. To better understand this variability, we applied single-cell transcriptomics to paired peripheral blood and pancreas samples from anti-mouse CD3-treated non-obese diabetic (NOD) mice. This analysis identified distinct gene signatures associated with therapy success or resistance, with consistent patterns across both compartments. Success-associated signatures were enriched in NK/CD8⁺ T cells as well as other immune cell types, whereas resistance signatures were predominantly expressed by neutrophils. The immune communities underlying these response signatures were largely confirmed in human whole-blood sequencing data from the AbATE study at 6 months, which assessed teplizumab therapy in stage 3 T1D. Furthermore, baseline expression profiling in both the human TN10 (stage 2) and AbATE (stage 3) cohorts identified immune signatures predictive of therapy response, T cell-enriched signatures in responders and neutrophil-enriched signatures in non-responders, highlighting the critical roles of both adaptive and innate immunity in determining teplizumab outcome. Using an elastic-net logistic regression model, we developed a 26-gene blood-based signature capable of predicting teplizumab response with high accuracy (average AUC = 0.97 across bootstrapped datasets). Together, these findings demonstrate the predictive potential of immune gene signatures and highlight the value of transcriptomic profiling in guiding individualized treatment strategies with teplizumab in T1D.
2025-09-16 | GSE307823 | GEO
Project description:Lung CD8⁺ T cells induced during chronic tuberculosis exhibit functional heterogeneity, comprising both effector and exhausted states. CD226 is the most differentially expressed gene distinguishing effector from exhausted CD8⁺ T cells. Functionally, CD226 serves as a costimulatory molecule that promotes recognition of Mtb-infected macrophages. Loss of CD226 expression correlates with the onset of CD8⁺ T cell exhaustion during tuberculosis.
2025-07-22 | GSE302813 | GEO
Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.
2008-06-16 | E-GEOD-9650 | biostudies-arrayexpress
Project description:TGFb signaling is a major pathway associated with poor clinical outcome in patients with
advanced metastatic cancers and non-response to immune checkpoint blockade, particularly in the immune-excluded tumor phenotype. While previous pre-clinical studies demonstrated that converting tumors from an excluded to an inflamed phenotype and curative anti-tumor immunity require attenuation of both PD-L1 and TGFb signaling, the underlying cellular mechanisms remain unclear. Recent studies suggest that stem cell-like CD8 T cells (TSCL) can differentiate into non-exhausted CD8 T effector cells that drive durable anti-tumor immunity. Here, we show that TGFb and PD-L1 restrain TSCL expansion as well as replacement of progenitor exhausted and dysfunctional CD8 T cells with non-exhausted IFNghi CD8 T effector cells in the tumor microenvironment (TME). Blockade of TGFb and PD-L1 generated IFNghi CD8 T effector cells with enhanced motility, enabling both their accumulation in the TME and increased interaction with other cell types. Ensuing IFNg signaling markedly transformed myeloid, stromal, and tumor niches to yield a broadly immune-supportive ecosystem. Blocking IFNg completely abolished the effect of anti-PD-L1/ TGFb combination therapy. Our data suggest that TGFb works in concert with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells with fresh CD8
T effector cells, thereby maintaining the CD8 T cell compartment in a dysfunctional state.
2023-06-16 | MSV000092193 | MassIVE