Single-cell clonal tracking of persistent T-cells in allogeneic hematopoietic stem cell transplantation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222633 | GEO | 2023/01/27
REPOSITORIES: GEO
Similar Datasets
Project description:A protein signature that could identify graft-versus-tumor (GVT) activity without graft-versus-host disease (GVHD), would allow for customized treatment plans following hematopoietic cell transplantation (HCT). Using orthogonal three-dimensional intact-protein analysis system (IPAS)
coupled with protein tagging and novel systems biology pipeline, we identified a signature of 49 proteins that are significantly increased in the plasma of HCT patients who received donor lymphocyte injection for tumor relapse and develop GVT without GVHD.
2017-05-03 | MSV000081057 | MassIVE
Project description:αβT cell- and B cell-depleted HLA-haploidentical haematopoietic stem cell transplantation is a life-saving therapeutic option to treat patients with high-risk leukemia. The G-CSF treatment stimulates mobilization from the bone marrow to blood of hematopoietic stem cells (HSC), and this manipulated graft also contains mature donor-derived NK and γδT cells, both exerting graft-versus-leukemia activity and control of infections at early stages after transplantation. The G-CSF-induced mobilization in the donor causes relevant increases of different myeloid cells, including polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). PMN-MDSC are present in high proportions in the graft and exert a sharp inhibition on the effector functions of co-infused mature NK cells. Conversely, low frequencies of PMN-MDSCs are detected in the blood of non-mobilized healthy donors. We used microarray technology to identify possible differences in the transcriptional programme of PMN-MDSCs isolated from blood of G-CSF mobilized donors as compared to those of non-mobilized healthy individuals.
2021-05-19 | GSE159069 | GEO
Project description:Abundant donor cytotoxic T cells that attack normal host organs remain a major problem for patients receiving allogeneic hematopoietic cell transplantation (Allo-HCT). Despite an increase in our knowledge of the pathobiology of acute graft versus host disease (aGvHD), the mechanisms regulating the proliferation and function of donor T cells remain unclear. Here, we show that activated donor T cells express galectin-3 (Gal-3) after allo-HCT. In both major and minor histocompatibility–mismatched models of murine aGvHD, expression of Gal-3 is associated with decreased T cell activation and suppression of the secretion of effector cytokines including IFN-γ and GM-CSF. Mechanistically, Gal-3 results in activation of NFAT signaling which can induce T cell exhaustion. Gal-3 overexpression in human T cells prevents severe disease by suppressing cytotoxic T cells in xenogeneic aGvHD models. Together these data identify the Gal-3-dependent regulatory pathway in donor T cells as a critical component of inflammation in aGvHD.
2023-03-13 | GSE225756 | GEO
Project description:The long-term viability of Pacific salmon stocks and the fisheries they support are threatened if large numbers die prematurely en-route to spawning grounds. Physiological profiles that were correlated with the fate of wild sockeye salmon during river migration were discovered using functional genomics studies on biopsied tissues. Three independent biotelemetry studies tracked the biopsied fish after tagging in the marine environment over 200 km from the Fraser River, in the lower river 69 km from the river mouth and at the spawning grounds. Salmon carrying the poor performance (unhealthy) profile in the ocean exhibited a 4-times lower probability of arriving to spawning grounds than those with a healthy genomic signature, although generally migrated into the river and to the spawning grounds faster. A related unhealthy signature observed in the river was associated with a 30% reduction in survival to spawning grounds in one of the three stocks tested. At spawning grounds, the same poor performance signature was associated with twice the pre-spawning mortality compared with healthy fish. Functional analysis revealed that the unhealthy signature, which intensified during migration to spawning grounds, was consistent with an intracellular pathogenic infection, likely a virus. These results are the first to suggest a pathogen present in salmon in the marine environment could be a major source of mortality during migration and spawning in the river. This series are gill expression profiles from the study of fish sampled and tagged in the lower river and tracked as they swam towards the spawning grounds. Fish were caught in seine nets, gastrically implanted with radio transmitters, and biopsy sampled for blood, gill, muscle, and fin. Individual fish were tracked by receivers placed throughout the Fraser River watershed to identify and fate (i.e. the location of the receiver that last detected the fish). Targeted stocks of interest were genetically identified. Gene expression was profiled in gill tissue, a critical respiratory and ionoregulatory organ that is highly responsive to stress, chemical exposure and disease. Gene expression was assayed on the GRASP salmonid 16K cDNA microarray.
2010-12-31 | E-GEOD-22177 | biostudies-arrayexpress
Project description:This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient’s immune system from rejecting the donor’s stem cells. Healthy stem cells from a donor that are infused into the patient help the patient’s bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body’s normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.
| 2112331 | ecrin-mdr-crc
Project description:The long-term viability of Pacific salmon stocks and the fisheries they support are threatened if large numbers die prematurely en-route to spawning grounds. Physiological profiles that were correlated with the fate of wild sockeye salmon during river migration were discovered using functional genomics studies on biopsied tissues. Three independent biotelemetry studies tracked the biopsied fish after tagging in the marine environment over 200 km from the Fraser River, in the lower river 69 km from the river mouth and at the spawning grounds. Salmon carrying the poor performance (unhealthy) profile in the ocean exhibited a 4-times lower probability of arriving to spawning grounds than those with a healthy genomic signature, although generally migrated into the river and to the spawning grounds faster. A related unhealthy signature observed in the river was associated with a 30% reduction in survival to spawning grounds in one of the three stocks tested. At spawning grounds, the same poor performance signature was associated with twice the pre-spawning mortality compared with healthy fish. Functional analysis revealed that the unhealthy signature, which intensified during migration to spawning grounds, was consistent with an intracellular pathogenic infection, likely a virus. These results are the first to suggest a pathogen present in salmon in the marine environment could be a major source of mortality during migration and spawning in the river. This series is of gill expression profiles from the study of fish sampled and tagged in the ocean and tracked as they entered the river system and swam towards the spawning grounds. Fish were caught in seine nets, gastrically implanted with radio transmitters, and biopsy sampled for blood, gill, muscle, and fin. Individual fish were tracked by receivers placed throughout the Fraser River watershed to identify and fate (i.e. the location of the receiver that last detected the fish). Targeted stocks of interest were genetically identified. Gene expression was profiled in gill tissue, a critical respiratory and ionoregulatory organ that is highly responsive to stress, chemical exposure and disease. Gene expression was assayed on the GRASP salmonid 16K cDNA microarray.
2010-12-31 | E-GEOD-22171 | biostudies-arrayexpress
Project description:The extent to which tissue-resident memory T (TRM) cells in transplanted organs possess alloreactivity is uncertain. This study investigates the alloreactive potential of TRM cells in kidney explants from four patients who experienced severe acute rejection leading to graft loss. Alloreactive T-cell receptors (TCRs) clones were identified in pre-transplant blood samples through mixed lymphocyte reactions, followed by single-cell RNA and TCR sequencing of the proliferated recipient T cells. Subsequently, these TCR clones were traced in the TRM cells of kidney explants, which were also subjected to single-cell RNA and TCR sequencing. The proportion of TRM cells expressing an alloreactive TCR in the four kidney explants varied from 0% to 9%. Notably, these alloreactive TCRs were predominantly found among CD4+ and CD8+ TRM cells with an effector phenotype. Intriguingly, alloreactive clones were present not only in recipient-derived TRM cells but also in donor-derived TRM cells, constituting up to 4% of the donor population, suggesting the presence of self-reactive TRM cells. Overall, our study demonstrates that T cells with alloreactive potential present in the peripheral blood prior to transplantation can infiltrate the kidney transplant and adopt a TRM phenotype.
2024-03-01 | GSE249197 | GEO
Project description:Allogeneic Vγ9Vδ2 (Vδ2) T cells are attractive candidates in the development of cancer therapies due to their demonstrated safety in allogeneic settings and innate ability to fight tumors. However, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor evasion. To address these limitations, we have generated Vδ2 T cells with improved properties. By utilizing CD16 as a donor selection biomarker, we have generated Vδ2 T cells with high levels of cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) function, and RNA sequencing characterization supports the increased effector function of Vδ2 T cells obtained from CD16 high (CD16Hi) donors. Further improvement was achieved through CAR and IL-15 engineering techniques. Preclinical studies in two ovarian cancer models showed that engineered CD16Hi Vδ2 T cells are both effective and safe, targeting tumors through multiple mechanisms, exhibiting long-term persistence in vivo, and not causing graft-versus-host disease. These findings support the potential of engineered CD16Hi Vδ2 T cells as a viable cancer therapy option.
2023-06-29 | GSE235755 | GEO
Project description:The long-term viability of Pacific salmon stocks and the fisheries they support are threatened if large numbers die prematurely en-route to spawning grounds. Physiological profiles that were correlated with the fate of wild sockeye salmon during river migration were discovered using functional genomics studies on biopsied tissues. Three independent biotelemetry studies tracked the biopsied fish after tagging in the marine environment over 200 km from the Fraser River, in the lower river 69 km from the river mouth and at the spawning grounds. Salmon carrying the poor performance (unhealthy) profile in the ocean exhibited a 4-times lower probability of arriving to spawning grounds than those with a healthy genomic signature, although generally migrated into the river and to the spawning grounds faster. A related unhealthy signature observed in the river was associated with a 30% reduction in survival to spawning grounds in one of the three stocks tested. At spawning grounds, the same poor performance signature was associated with twice the pre-spawning mortality compared with healthy fish. Functional analysis revealed that the unhealthy signature, which intensified during migration to spawning grounds, was consistent with an intracellular pathogenic infection, likely a virus. These results are the first to suggest a pathogen present in salmon in the marine environment could be a major source of mortality during migration and spawning in the river. This series are gill expression profiles from the study of fish sampled and tagged in the lower river and tracked as they swam towards the spawning grounds.
2010-12-31 | GSE22177 | GEO
Project description:Tissue resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, while their establishment and role in human tissues has been difficult to assess. Here, we investigated human lung TRM generation, maintenance and function in airway samples obtained longitudinally from HLA-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, while lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes while recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared to recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide novel spatial and temporal insights into how human TRM develop, function, persist, and impact tissue integrity within the complexities of lung transplantation.
2019-04-03 | GSE124675 | GEO