Vitamin C and cancer

Could vitamin C hold the key to improving the efficacy of dendritic cell-based anti-cancer therapies?

Researchers from the Epigenetics and Immune Diseases Laboratory of the Josep Carreras Leukemia Research Institute in Badalona, ​​a CERCA center of the Government of Catalonia, have shown that vitamin C improves the immunogenic properties of dendritic cells, in vitro. The results show that the treatment of cells with vitamin C leads to a more constant activation of genes involved in the immune response, mainly through DNA demethylation, a type of epigenetic reprogramming. This discovery may be useful for generating more powerful dendritic cell-based therapies in the future.

Since the inception of cancer cell therapies, which use living cells to find and kill tumors, many types of immune cells have been used. The best known cell therapies use lymphocytes, as in the successful CAR-T therapies. Recently, dendritic cells have attracted the attention of scientists due to their ability to capture and present antigens (small parts of a pathogen or cancer cell) to T cells, and induce powerful antigen-specific immune activation. In this sense, loading dendritic cells with specific antigens to create an immune memory forms the basis of the so-called DC vaccines.

To study dendritic cells in the lab, researchers differentiate them from monocytes (also a type of immune cell) using a particular set of molecular signals. This differentiation is achieved through a complex set of gene activation processes in the cell nucleus, mainly thanks to the activity of the chromatin remodeling machinery headed by the TET family of demethylases, proteins that act on the epigenetic marks of the cell. DNA.

Vitamin C was known to interact with several TET family proteins enhancing their activity, but the specific mechanism was not yet well understood in human cells. In a new study, a team led by Dr. Esteban Ballestar has hypothesized that treating monocytes in vitro while they differentiate into dendritic cells would help the resulting cells become more mature and active.

The results obtained by the team that includes Octavio Morante-Palacios, first author of the study, José Luis Sardina (also from the Josep Carreras Leukemia Research Institute) and Eva Martínez-Cáceres, head of Immunology at the Germans Trias Research Institute i Pujol show that vitamin C treatment triggers extensive demethylation at NF-kB/p65 binding sites, compared to untreated cells, promoting 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, the researchers showed that dendritic cells stimulated with vitamin C and loaded with antigens specific for the SARS-CoV-2 virus were able to activate T cells in vitro more efficiently than untreated cells, demonstrating the superiority of vitamin-treated DC vaccines. c.

Members of Ballestar’s lab. (Photo: Josep Carreras Leukemia Research Institute)

Taken together, these new findings support the hypothesis that treatment of vitamin C-treated monocyte-derived dendritic cells may help generate higher-yielding DC vaccines. After consolidating these results in preclinical models and, if necessary, in clinical trials, a new generation of cell therapies based on dendritic cells could be developed that can be used in the clinical setting to combat cancer more effectively.

The study is titled “Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells”. And it has been published in the academic journal Nucleic Acids Research. (Source: Josep Carreras Leukemia Research Institute)