Dendritic cells from fibroblasts
Skin cells turned into immune cells
The authors suggest using the invented mechanism to fight cancer
Alexey Yevglevsky, Naked Science
A research team from Lund University (Sweden) has successfully reprogrammed human skin cells into immune cells called dendritic cells for the first time. The work was published in the journal Science Immunology (Rosa et al., Direct reprogramming of fibroblasts into antigen-presenting dendritic cells).
Dendritic cells are heterogeneous cells of bone marrow origin involved in the work of immunity. Their function is to "scan" body tissues to detect viruses, bacteria and cancer cells. They mark pathogen molecules as antigens (hostile to immunity), after which T-lymphocytes recognize the enemy and attack.
Based on the behavior of dendritic cells, scientists tried to create a way to fight cancer, but the tumor attacked the cells in such a way that they lost their function. Therefore, the authors were looking for artificial ways to obtain dendritic cells. Analyzing their transcription factors, they identified three proteins (PU.1, IRF8, BATF3) that are necessary for the transformation of fibroblasts (connective tissue cells) of mice and humans into dendritic cells.
They noted that this process can be individual for each person, and reprogramming takes only nine days. In vitro experiments have shown that grown dendritic cells behave like natural ones.
The first author of the article, Carlos Filipe Pereira, explained what application the technology can find:
"Tumors often undergo a series of mutations, turning into a heterogeneous unit, which makes it difficult for the immune system to respond. In the longer term, we plan to investigate the process of reprogramming dendritic cells for the development of gene therapy against cancer. We are going to inject three key proteins directly into the tumor, so that it itself represents antigens specific to this cancer. This will set the attacking immune cells against cancer cells and destroy them. We called this concept TrojanDC."
Recall that the 2018 Nobel Prize in Medicine was awarded for a discovery in the treatment of cancer. Immunologists James Ellison from the USA and Tasuku Honjo from Japan were awarded for the method of cancer treatment by suppressing negative immune regulation. Thanks to their contribution, cancer therapy with immune response checkpoint inhibitors has become possible.
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