Effectively target cancer cells with natural killer immune cells. It is the mechanism underlying theimmunotherapy That uses the body’s immune system to attack cancer cells and that has become a powerful tool to combat the cancer. But, for unclear reasons, tumors evade immune cells, and are often resistant to these therapies. A new study conducted by Italian researchers of the Fox Chase Cancer Center of Philadelphia shows as a process called DNA methylation may regulate the immune response in colorectal cancer.
DNA methylation and demethylation are two molecular processes, the correct functioning of which regulates genes turning on and off: Methylation turns them off, while demethylation turns them back on. “By blocking the demethylation process, we can make cancer cells very sensitive to being eliminated by natural killer immune cells,” explains the study coordinator. Alfonso Bellacosaa professor in the Nuclear Dynamics & Cancer research program and a member of the Cancer Epigenetics Institute at the Fox Chase Cancer Center.
Colon cancer, how demethylation works
In the colorectal cancer, one of the tumors with the highest incidence in the world and which in Italy has more than 40,000 new cases a year, the importance of DNA methylation was already known, but what its role at the molecular level was not known. The researchers therefore conducted a study aimed at better understanding this mechanism, in order to improve the diagnosis and therapy of this cancer: studying colon tumors of mice lacking enzymes involved in demethylation, they found that these tumors had higher levels of methylation throughout the genome – but especially in regions called ‘CpG islands’ – of a group of genes that regulate the immune response.
Furthermore, these tumors (termed CIMP, due to methylation of CpG islands) had increased inflammation and interferon response, processes that play a key role in the immune system’s ability to identify and attack ‘diseased’ cells. “When this happens, tumors are more visible and better detected by the immune system – highlights Bellacosa – So the immune cells are able to infiltrate tumors more easily”.
Active DNA demethylation (TET1/TDG) suppresses CRC inflammatory/INF response. CIMPs show an imbalance; high DNMT1 and low TET1. relevant to cancer #immunotherapy by my friend and colleague #AlfonsoBellacosa @FoxChaseCancer @CeiFccc
— Dr. Edna Cukierman, Ph.D. (@ednacukierman) February 27, 2023