Background: Active dendritic cell (DC) immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML). Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR) agonists in intensively pretreated patients with AML.
Methods: Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls.
Results: Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C), induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70), showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells.
Conclusions: Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.
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http://dx.doi.org/10.1186/1479-5876-9-151 | DOI Listing |
Am J Hematol
January 2025
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
We retrospectively analyzed a large international cohort of 1113 patients with aplastic anemia to evaluate treatment choice and outcome in elderly patients as compared with a younger population. Overall, 319 (29%) patients were > 60 years old at diagnosis (60-64 years (n = 85), 106 65-69 years (n = 106), and 128 > 70 years (n = 128)). Elderly patients showed a more severe thrombocytopenia at onset and a significantly lower overall response (complete plus partial) to first-line therapy at 6 months as compared to younger patients (47% vs.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
Introduction: DNA methylation inhibitors have been approved for the prevention of Acute Myeloid Leukemia (AML), and their safety profile is not fully characterized. This study was aimed at evaluating the adverse drug reactions (ADRs) of DNA methylation inhibitors by analyzing the individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database.
Materials And Methods: The EV database managed by the European Medicines Agency was adopted.
Front Cell Dev Biol
January 2025
Department of Hematology, Jiangdu People's Hospital, Yangzhou, China.
Introduction: Acute myeloid leukemia (AML), a highly heterogeneous hematological malignancy, remains a major challenge in adult oncology. Stem cell research has highlighted the crucial role of long noncoding RNA (lncRNA) in regulating cellular differentiation and self-renewal processes, which are pivotal in AML pathogenesis and therapy resistance.
Methods: This study explores the relationship between cuproptosis-related lncRNAs and AML prognosis, providing novel insights into their impact on hematopoietic stem and progenitor cells.
Eur J Haematol
January 2025
Hematology, St. Paul's Hospital and The University of British Columbia, Vancouver, British Columbia, Canada.
Introduction: Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.
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