A team of researchers from the Laboratory of Epigenetics and Immune Diseases at the Josep Carreras Research Institute for Leukemia Diseases recently showed that vitamin C improves the immunogenicity of dendritic cells in vitro. Recently published results show that treating cells with vitamin C leads to a more uniform activation of genes involved in the immune response, mainly through DNA demethylation, a type of epigenetic reprogramming. This discovery could be useful in the future to generate more effective dendritic cell-based therapies.
Since the introduction of cancer cell therapies, which use living cells to search for and eliminate tumors, many types of cells of the immune system have been used. The best-known cell therapies use lymphocytes, as in the highly successful CAR-T therapies. Recently, dendritic cells have attracted the attention of scientists due to their ability to take up and present antigens (small fragments of a pathogen or tumor cell) to T cells, which induces a concentrated activation of the immune system in response to a given antigen. In this context, the loading of dendritic cells with specific antigens to generate an immune memory is called DC vaccines.
To study dendritic cells in the lab, researchers differentiate them from monocytes (also immune cells) using a specific set of molecular signals. This differentiation is achieved through a complex process of gene activation in the cell nucleus, mainly due to the activity of the chromatin remodeling machinery, which consists primarily of TET family demethylase proteins, acting on epigenetic DNA markers.
Vitamin C was known to interact with several TET proteins to enhance their activity, but the exact mechanism of action in human cells remained poorly understood. In a recent publication in the journal Nucleic Acids Research, a team led by Dr. Esteban Ballestar assumed that in vitro treatment of monocytes during differentiation into dendritic cells would allow for more mature and active cells.
The results obtained by Octavio Morante-Palacios, first author of the paper, José Luis Sardina (also from the Josep Carreras Research Institute for Leukemia Diseases) and Eva Martínez-Cáceres, Head of Immunology at the Germans Trias i Pujol Research Institute, show that treatment with vitamin C causes an extensive demethylation of NF-kB/p65 binding sites compared to untreated cells, which promotes the activity of genes involved in antigen presentation and activation of the immune response. In addition, vitamin C increases the communication of the resulting dendritic cells with other components of the immune system and stimulates the proliferation of antigen-specific T cells.
In fact, researchers demonstrated that vitamin C-stimulated dendritic cells loaded with SARS-CoV-2 virus-specific antigens were able to activate T cells in vitro more effectively than untreated cells, demonstrating the superiority of vitamin C-treated DC vaccines.
Taken together, these new findings support the hypothesis that treating monocytic dendritic cells with vitamin C can help generate higher yield DC vaccines. Once these results have been confirmed in preclinical models and hopefully in clinical trials, a new generation of dendritic cell-based cell therapies could be used in the clinic to combat cancer more effectively.
