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Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing.
Neuron
January 2025
Molecular Neuroregeneration, Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK. Electronic address:
Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.
View Article and Find Full Text PDFAcute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.
medRxiv
December 2024
Program in Immunology, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8 T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (T). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific T did not clearly improve outcomes in fifteen patients with active disease post-HCT.
View Article and Find Full Text PDFOvercoming effector T cell exhaustion in ovarian cancer ascites with a novel adenovirus encoding for a MUC1 bispecific antibody engager and IL-2 cytokine.
Mol Ther
September 2024
Cancer Gene Therapy Group, Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; TILT Biotherapeutics Ltd, Helsinki, Finland; Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, Helsinki, Finland; Helsinki University Hospital (HUS), Comprehensive Cancer Center, Helsinki, Finland. Electronic address:
T cell-focused cancer immunotherapy including checkpoint inhibitors and cell therapies has been rapidly evolving over the past decade. Nevertheless, there remains a major unmet medical need in oncology generally and immuno-oncology specifically. We have constructed an oncolytic adenovirus, Ad5/3-E2F-d24-aMUC1aCD3-IL-2 (TILT-322), which is armed with a human aMUC1aCD3 T cell engager and IL-2.
View Article and Find Full Text PDFStudying the cellular basis of small bowel enteropathy using high-parameter flow cytometry in mouse models of primary antibody deficiency.
Front Immunol
May 2024
Pathology, Microbiology, and Immunology Department, University of South Carolina School of Medicine, Columbia, SC, United States.
Background: Primary immunodeficiencies are heritable defects in immune system function. Antibody deficiency is the most common form of primary immunodeficiency in humans, can be caused by abnormalities in both the development and activation of B cells, and may result from B-cell-intrinsic defects or defective responses by other cells relevant to humoral immunity. Inflammatory gastrointestinal complications are commonly observed in antibody-deficient patients, but the underlying immune mechanisms driving this are largely undefined.
View Article and Find Full Text PDFInvariant γδTCR natural killer-like effector T cells in the naked mole-rat.
Nat Commun
May 2024
Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
The naked mole-rat (Heterocephalus glaber) is a long-lived rodent species showing resistance to the development of cancer. Although naked mole-rats have been reported to lack natural killer (NK) cells, γδ T cell-based immunity has been suggested in this species, which could represent an important arm of the immune system for antitumor responses. Here, we investigate the biology of these unconventional T cells in peripheral tissues (blood, spleen) and thymus of the naked mole-rat at different ages by TCR repertoire profiling and single-cell gene expression analysis.
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