New therapies are highly needed to stabilize remission in patients with acute myeloid leukemia (AML). This study investigates the value of dendritic cells derived from leukemic blasts (DC) to enhance anti-leukemic immunity after T-cell-enriched mixed lymphocyte cultures (MLCs). We correlated induced anti-leukemic activity with patient data, including biological, clinical and prognostic factors. Additionally, we correlated the frequencies of DC/DC and leukemic-specific T cells with the achieved anti-leukemic activity after MLC. We show that mature DC/DC can be generated using the immunomodulating Kit-M, which contains granulocyte-macrophage colony-stimulating-factor (GM-CSF) and prostaglandin E (PGE), without inducing blast proliferation from leukemic whole blood (WB) samples. Activated leukemia-specific immune and memory cells increased after MLC with Kit-M-pretreated WB, leading to improved blast lysis. Enhanced anti-leukemic activity positively correlated with the frequencies of generated DC/DC, proliferating leukemic-specific T cells and memory T cells, but not with leukemic blast counts, hemoglobin levels or platelet counts at diagnosis. No correlation was found between improved blast lysis and patients' prognostic data, including age, gender, ELN risk groups, disease stage and response to induction chemotherapy. These findings underscore the potential of DC/DC to evoke robust immune responses and potential immunological memory against AML. Overall, this innovative approach could pave the way for the development of improved immunotherapeutic strategies that function in vivo.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855365 | PMC |
http://dx.doi.org/10.3390/ijms26041700 | DOI Listing |
Donor Lymphocyte Infusion (DLI) is a crucial therapeutic strategy for relapsed myeloid malignancies post-allogeneic hematopoietic cell transplantation (allo-HCT), leveraging the graft-versus-leukemia (GvL) effect to restore immune control. While highly effective in chronic myeloid leukemia (CML), its efficacy in acute myeloid leukemia (AML) remains limited, with underlying mechanisms not fully understood. Recent research by Maurer and colleagues utilized cutting-edge technologies to dissect immune-leukemia interactions within the bone marrow niche, identifying a cytotoxic CD8+ T cell population as a key mediator of the anti-leukemic response.
View Article and Find Full Text PDFFront Immunol
March 2025
Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China.
Introduction: Natural killer (NK) cells, which exert spontaneous cytotoxicity against infectious diseases and cancer, also play an important role in leukemia therapy. Despite the success of NK-based therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in these hematologic malignancies remains elusive. The aim of the present study was to investigate whether allogeneic NK cells combined with aclacinomycin (ACM) could enhance anti-leukemic functionality against an acute myeloid leukemia (AML) cell line and to clarify the underlying mechanism.
View Article and Find Full Text PDFMol Ther Oncol
March 2025
Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hematopoietic stem cell transplantation (HSCT) is the only definitive cure for pediatric acute myeloid leukemia (AML). Despite adjustments in HSCT protocols and improvements in supportive care, 30% of high-risk patients who receive HSCT as part of their therapy still experience disease relapse with high transplant-related mortality. Relapsed AML has a dismal prognosis, and novel therapies are needed.
View Article and Find Full Text PDFInt J Mol Sci
February 2025
Department of Medicine III, University Hospital of Ludwig-Maximilian-University Munich, 81377 Munich, Germany.
New therapies are highly needed to stabilize remission in patients with acute myeloid leukemia (AML). This study investigates the value of dendritic cells derived from leukemic blasts (DC) to enhance anti-leukemic immunity after T-cell-enriched mixed lymphocyte cultures (MLCs). We correlated induced anti-leukemic activity with patient data, including biological, clinical and prognostic factors.
View Article and Find Full Text PDFJ Clin Invest
February 2025
Departments of Pediatrics and Cancer Biology, Cleveland Clinic, Cleveland, United States of America.
Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency, and bony abnormalities with an increased risk of myeloid neoplasia. Almost all cases of SDS result from biallelic mutations in SBDS. SBDS interacts with EFL1 to displace EIF6 from the 60S ribosomal subunit.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!