Researchers have discovered a key mechanism by which radiation treatment (radiotherapy) fails to completely destroy tumors. And, in the journal Nature Immunology, they offer a novel solution to promote successful radiotherapy for the millions of cancer patients who are treated with it.

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 to even trigger an immune response causing skin tumors such as melanoma, to resist further treatment.

Investigators mimicked the effect of immunotherapy drugs called "immune checkpoint inhibitors" to boost the immune system to attack tumors. 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.

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.

While this study was conducted using mouse models of melanoma and focused on the skin where these Langerhans cells are located, the researchers believe the same process happens in organs throughout the body. There, cousins of Langerhans cells called dendritic cells are also activated by radiotherapy and the investigators stressed that it is critical we understand how they respond to treatment as well.

http://www.mountsinai.org/about-us/newsroom/press-releases/researchers-discover-how-immune-cells-resist-radiation-treatment