Up to 60 percent of cancer patients receive radiation therapy, but it's not always effective. These treatments fail because the tumor grows back at the site of the original tumor, or the tumor metastasizes to another part of the body. A new study from University of Chicago hopes to overcome resistance to radiation therapy by inhibiting a key protein, bringing the immune system into the fight.

The study, published in the May 25 issue of Cancer Cell, shows how drug therapy that inhibits YTHDF2 (or Y2) improves outcomes with radiation therapy alone or in combination with immunotherapy. YTHDF2 is a protein that suppresses the immune response after radiation therapy. This treatment also prevented the progression of distant metastases after local radiotherapy, making Y2 a promising target for future combination therapy programs.

Professor Ralph Weichselbaum of the University of Chicago said, "These findings have potential clinical implications because not only can we enhance the local effects of radiation, but we can also eliminate these adverse long-range effects of radiation, and I think these findings may change the practice of radiation therapy."

Radiation therapy sometimes produces what is known as an abscopal effect, in which radiation to one part of the tumor also causes the tumor in another part of the body to shrink. This phenomenon is rare, but it is thought to be related to the activation of the immune system. Radiation stimulates positive immune effects, such as the generation of more antigen-presenting cells and CD8+ T cells, as well as the negative effects of suppressing antitumor immune responses. A type of blood cell called myeloid-derived suppressor cells (MDSCs) migrates to the tumor site and dampens the antitumor immune response by blocking the antitumor effects of CD8+ T cells. The influx of MDSCs can also interfere with immunotherapy, which aims to unleash the immune system to fight tumors.