Researchers from the Epigenetics and Immune Illness Lab on the Josep Carreras Leukaemia Analysis Institute have lately proven that vitamin C improves the immunogenic properties of dendritic cells in vitro.
The group’s outcomes, lately revealed in Nucleic Acids Analysis, present that treating the cells with vitamin C results in a extra constant activation of genes concerned within the immune response, primarily via DNA demethylation, a type of epigenetic reprogramming. This discovery could also be helpful for producing stronger dendritic cell-based therapies sooner or later.
Because the onset of anticancer cell therapies, which use dwelling cells to seek out and eradicate tumors, many varieties of immune cells have been used. The most effective-known cell therapies use lymphocytes, as in extremely profitable CAR-T therapies.
Just lately, dendritic cells have attracted scientists’ consideration, as a result of their potential to uptake and current antigens (small components of a pathogen or a most cancers cell) to T-lymphocytes and induce an antigen-specific potent immune activation. On this regard, loading dendritic cells with particular antigens to create immune reminiscence constitutes so-called DC vaccines.
To check dendritic cells within the lab, researchers differentiate them from monocytes (additionally an immune cell) utilizing a specific kind of molecular signaling. This differentiation is achieved via a posh set of gene activation processes within the nucleus, largely as a result of exercise of the chromatin reworking equipment spearheaded by the TET household of demethylases, proteins that act upon the DNA epigenetic marks.
Vitamin C was identified to work together with a number of TET proteins to reinforce its exercise, however the particular mechanism was nonetheless poorly understood in human cells. Within the Nucleic Acids Analysis research, a group lead by Dr. Esteban Ballestar hypothesized that treating monocytes in vitro through the dendritic cell differentiation course of would assist the ensuing cells be extra mature and energetic.
The outcomes obtained by Octavio Morante-Palacios, first writer of the publication, José Luis Sardina (additionally from the Josep Carreras Leukaemia Analysis Institute) and Eva Martínez-Cáceres, Head of Immunology of the Germans Trias i Pujol Analysis Institute, present that vitamin C remedy triggers an intensive demethylation at NF- kB/p65 binding websites in contrast with non-treated cells, selling the exercise of genes concerned in antigen presentation and immune response activation. Vitamin C additionally will increase the communication of the ensuing dendritic cells with different parts of the immune system and stimulates the proliferation of antigen-specific T cells.
Moreover, the researchers proved that vitamin C-stimulated dendritic cells loaded with antigens particular to the SARS-CoV-2 virus extra effectively activated T cells in vitro than did non-treated cells, displaying the prevalence of DC vaccines handled with vitamin C.
General, these new findings help the speculation that treating monocyte-derived dendritic cells with vitamin C could assist generate DC vaccines with greater efficiency. After consolidating these ends in preclinical fashions, and hopefully in scientific trials, a brand new era of cell therapies primarily based on dendritic cells might be used within the clinic to struggle most cancers extra effectively.
Octavio Morante-Palacios et al, Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells, Nucleic Acids Analysis (2022). DOI: 10.1093/nar/gkac941
Vitamin C could maintain the important thing to enhance efficacy of dendritic cell-derived anticancer cell therapies (2022, November 2)
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