Immunotherapy is one of the pillars in the fight against cancer and aims to enable the body’s own immune system to fight a tumor. A recent study now shows that removing certain enzymes that regulate epigenetic processes from the so-called dentate cells of the immune system affects their development and therefore improves anti-tumor immunity. This finding could lead to new therapeutic strategies in immunotherapy. The study by Cristiano De Sá Fernandes from Maria Sibilia’s research group at the Center for Cancer Research and Comprehensive Cancer Center of MedUni Vienna and Vienna General Hospital was recently published in Cell Reports.
Cancer cells are the body’s own cells that do not divide and grow as intended and give up their place and function in the body. The difficult thing about fighting them is that, as the body’s own cells, the immune system cannot recognize them well and therefore cannot fight them. This is where immunotherapy comes in: It enables the patient’s own immune system to recognize cancer cells and activate the body’s own defenses.
Dendritic cells (DCs) are important cells of the immune system that develop from progenitor cells and can form different subsets by changing their gene activity. These subgroups perform different functions in the immune system. However, it is not yet known exactly how certain epigenetic changes in chromatin (the material that makes up chromosomes) affect the development of DCs. In the study, the researchers inhibited two enzymes that regulate such epigenetic processes to see how this affects the growth and function of DCs. They focused on the specific enzymes HDAC1 and HDAC2.
Improved immune response
Through multi-omics analyses, i.e. the analysis of many biological data, such as gene expression and chromatin accessibility, the researchers found that the growth of certain subsets of DCs was affected by the absence of HDAC1. This indicates that HDAC1 plays a key role in their development. In the absence of HDAC1, DCs alter their immune response, which improves tumor surveillance. Deletion of the HDAC2 enzyme, on the other hand, had no significant effect on the growth of DCs.
In summary, the study shows that ablation of HDAC1 affects the development of certain DC subsets and improves antitumor immunity. These findings could lead to new therapeutic strategies in cancer immunotherapy.
This study was conducted as part of the FWF DocFunds funded PhD program “Tissue Home”, the first author Cristiano de Fernandes was a PhD student.
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Journal Reference:
De Sá Fernandes, C., et al. (2024). Histone deacetylase HDAC1 controls dendritic cell development and antitumor immunity. Cell references. doi.org/10.1016/j.celrep.2024.114308.
