Given the recent advancements of immune checkpoint inhibitors, there is considerable interest in cancer immunotherapy provided through dendritic cell (DC)-based vaccination. Although many studies have been conducted to determine the potency of DC vaccines against cancer, the clinical outcomes are not yet optimal, and further improvement is necessary. In this study, we evaluated the potential ability of human platelet lysate (HPL) to produce interferon-α-induced DCs (IFN-DCs). In the presence of HPL, IFN-DCs (HPL-IFN-DCs) displayed high viability, yield, and purity. Furthermore, HPL-IFN-DCs displayed increased CD14, CD56, and CCR7 expressions compared with IFN-DCs produced without HPL; HPL-IFN-DCs induced an extremely higher number of antigen-specific cytotoxic T lymphocytes (CTLs) than IFN-DCs, which was evaluated with a human leukocyte antigen (HLA)-restricted melanoma antigen recognized by T cells 1 (MART-1) peptide. Additionally, the endocytic and proteolytic activities of HPL-IFN-DCs were increased. Cytokine production of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α was also elevated in HPL-IFN-DCs, which may account for the enhanced CTL, endocytic, and proteolytic activities. Our findings suggest that ex-vivo-generated HPL-IFN-DCs are a novel monocyte-derived type of DC with high endocytic and proteolytic activities, thus highlighting a unique strategy for DC-based immunotherapies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823331PMC
http://dx.doi.org/10.3390/vaccines9010010DOI Listing

Publication Analysis

Top Keywords

endocytic proteolytic
12
proteolytic activities
12
human platelet
8
platelet lysate
8
cytotoxic lymphocytes
8
hpl-ifn-dcs displayed
8
hpl-ifn-dcs
6
interferon-α-induced dendritic
4
dendritic cells
4
cells generated
4

Similar Publications

The Type III Intermediate Filament Protein Peripherin Regulates Lysosomal Degradation Activity and Autophagy.

Int J Mol Sci

January 2025

Department of Experimental Medicine, University of Salento, Via Provinciale Lecce-Monteroni n. 165, 73100 Lecce, Italy.

Peripherin belongs to heterogeneous class III of intermediate filaments, and it is the only intermediate filament protein selectively expressed in the neurons of the peripheral nervous system. It has been previously discovered that peripherin interacts with proteins important for the endo-lysosomal system and for the transport to late endosomes and lysosomes, such as RAB7A and AP-3, although little is known about its role in the endocytic pathway. Here, we show that peripherin silencing affects lysosomal abundance but also positioning, causing the redistribution of lysosomes from the perinuclear area to the cell periphery.

View Article and Find Full Text PDF

Endocytosis mediated by megalin and cubilin is involved in enamel development.

Dev Dyn

January 2025

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Background: Endocytosis of enamel matrix proteins (EMPs) by ameloblasts is a key process in the mineralization of enamel during the maturation stage of amelogenesis. However, the relevant receptor mediating endocytosis of EMPs is still unclear. The aim of this study was to explore potential endocytic receptors involved in this process.

View Article and Find Full Text PDF

Unlabelled: Proteolysis of hydrophobic helices is required for complete breakdown of every transmembrane protein trafficked to the lysosome and sustains high rates of endocytosis. However, the lysosomal mechanisms for degrading hydrophobic domains remain unknown. Combining lysosomal proteomics with functional genomic data mining, we identify Lysosomal Leucine Aminopeptidase (LyLAP; formerly Phospholipase B Domain-Containing 1) as the hydrolase most tightly associated with elevated endocytic activity.

View Article and Find Full Text PDF

The evolutionarily conserved Notch signaling pathway controls cell-cell communication, enacting cell fate decisions during development and tissue homeostasis. Its dysregulation is associated with a wide range of diseases, including congenital disorders and cancers. Signaling outputs depend on maturation of Notch receptors and trafficking to the plasma membrane, endocytic uptake and sorting, lysosomal and proteasomal degradation, and ligand-dependent and independent proteolytic cleavages.

View Article and Find Full Text PDF

Despite recent advances in mammalian synthetic biology, there remains a lack of modular synthetic receptors that can robustly respond to soluble ligands and, in turn, activate bespoke cellular functions. Such receptors would have extensive clinical potential to regulate the activity of engineered therapeutic cells, but so far only receptors against cell-surface targets have approached clinical translation. To address this gap, here we adapt a receptor architecture called the synthetic intramembrane proteolysis receptor (SNIPR) for activation by soluble ligands.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!