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Objectives: In this study, immature dendritic cells (imDCs) were transfected with the Bacillé Calmette-Guérin (BCG) heat shock protein 70 (HSP70) gene to investigate the impact on the maturity and function of imDCs from the bone marrow of pediatric patients with acute leukemia.
Materials And Methods: Bone marrow mononuclear cells were isolated from pediatric patients with acute lymphoblastic leukemia who had achieved complete remission at least 6 months prior. The recombinant vector pDisplay-HSP70 was transfected into imDCs. The test groups included 5 subgroups: imDCs (imDCs without special processing), imDC-neos (imDCs transfected with the pDisplay vector), HSP70 (imDCs transfected with the pDisplay-HSP70 vector), tumor necrosis factor α (TNF-α) (imDCs induced with rhTNF-α), and HSP70+TNF-α. Mature dendritic cells (mDCs) from different groups (HSP70, TNF-α, and HSP70+TNF-α) and T cells were cultured. An equal number of lymphocytes and mDCs were used as controls. The proliferation indices of T cells and the cytokine contents (interleukin-12 and interferon-γ) were determined.
Results: The HSP70 group and the TNF-α group expressed higher levels of HLA-DR, CD80, and CD86 but lower levels than the HSP70+TNF-α group; there was no significant difference between the HSP70 group and the TNF-α group. The combination of HSP70 and TNF-α induced the highest levels of interleukin-12 and interferon-γ.
Conclusions: The outcomes of this study indicated that gene transfection with BCG HSP70 evidently promoted imDC maturity and the antitumor effects of mDC-mediated T cells. It could serve as a candidate gene-modified cell vaccine for tumor immunotherapy.
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http://dx.doi.org/10.1097/MPH.0000000000002479 | DOI Listing |
J Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFAAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
View Article and Find Full Text PDFNature
September 2025
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE). Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 (PLD4). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays.
View Article and Find Full Text PDFJ Neurosci
September 2025
Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada, B3H4R2
At the glutamatergic synapses between rod photoreceptors and ON-type bipolar cells, neurotransmitter is detected by the postsynaptic metabotropic glutamate receptor mGluR6. This receptor forms trans-synaptic interactions with ELFN1, a presynaptic cell adhesion molecule expressed in rods, and ELFN1 is important for mGluR6 localization at bipolar cell dendritic tips. Here, we show that in mice of either sex lacking mGluR6, the presynaptic localization of ELFN1 is disrupted.
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