0341 GMT July 22, 2019
The team found that when radiotherapy damages skin harboring tumors, special skin immune cells called Langerhans cells are activated. These Langerhans cells can uniquely repair the damage in their own DNA caused by radiotherapy, allowing them to become resistant to radiotherapy and even trigger an immune response causing skin tumors such as melanoma, to resist further treatment, EurekAlert said.
Investigators mimicked the effect of immunotherapy drugs called ‘immune checkpoint inhibitors’ to boost the immune system to attack tumors. This in turn blocked the ability of Langerhans cells to repair their own DNA after radiotherapy causing them to die, preventing an immune response that protects skin tumors.
"Our study suggests that this combination approach — combining radiotherapy with drugs that rev up a healthy immune response — will help make radiation therapy much more effective," said the study's lead author, Immunologist Jeremy Price.
Ionizing radiation is a powerful therapeutic tool that causes toxic breaks in cellular DNA. The formation of these breaks triggers a response in Langerhans cells (which are usually dormant) to stop further damage and to repair the breaks.
The researchers discovered that when the skin is damaged by ionizing radiation, Langerhans cells travel to nearby lymph nodes to communicate with other immune cells and help program a population of regulatory T cells that dampen the immune system. These regulatory T cells then travel back to the damaged tumor, and shield it from attack by the immune system.
"We found melanoma grew much more quickly on mice pretreated with radiation, compared to untreated mice, because of the presence of regulatory T cells activated by Langerhans cells," Dr. Price said. "These Langerhans cells were resistant to radiation."
The researchers also discovered that Langerhans cells are able to resist lethal doses of radiation because they express very high levels of an important protein involved in the stress response that orchestrates DNA repair after radiotherapy.