Focused radiation may help turn on the immune system

meterMuch of the buzz around doctors’ ability to harness the power of the immune system to fight cancer has focused on targeted therapies — drugs designed to target specific properties of cancer cells, disrupting their signals and exposing them to immune attack. Now, researchers are discovering that these and other immunotherapy drugs can be even more powerful when combined with conventional treatments such as chemotherapy. “We’re finding ways to strengthen the immune system through drug combinations,” says Christian Hyde, MD, a radiation oncologist at Atlanta Hospital. But this tactic has limits: Mixing too many drugs often leads to significant side effects, such as autoimmune diseases, that can make these combinations impractical. Nevertheless, the group shows exciting and promising results, although it is still considered rare.

Absolute effect

The scientists were so intrigued that they gave the result a pseudonym: the absolute effect, which is derived from the combination (correct) of two words: ab , which in Latin means “far” and scopos, which in Greek means “objective”. The effect, first reported about 50 years ago, is rare and appears in a small number of patients undergoing radiotherapy for metastatic disease or metastatic cancer. In these unique cases, when radiation damages cancer cells, the tumor releases proteins called antigens that are recognized as harmful or foreign and are attacked by T cells of the immune system. This also helps the T cells to recognize and attack cancer cells in other parts of the body. The absolute effect is rare because radiation also tends to increase production of regulatory T cells, which prevent killer T cells from doing their job excessively as part of a self-regulatory process that stops the immune response before it causes too much damage. the body.

“Think of a timer in a hot tub. If you set it for 15 minutes, you’ll turn it on, but it also imposes a limit because if you don’t, you’ll end up wasting a lot of energy and you risk overheating.” Christian Hyde, radiation oncologist

Researchers have found that radiation given in medium to high doses over the course of three to five treatments affects the type of biological chord that activates the immune system. “This appears to be what it takes to wake up the immune system and make the tumor swollen so that it becomes a more fertile ground for immune activity,” says Dr. Hyde. “Radiation makes cancer cells look and act like virus-infected cells.” When the patient is taking an immunotherapy drug such as ipilimumab ( ^Yervoy®) Before and during radiation, it can help reduce the number of regulating T cells, which amplifies the immune response to affect other parts of the body, says Dr. Hyde. However, blocking a road, similar to blocking a lane to traffic on a highway, is not enough. Currently, single drug combinations with radiation increase the immune response. But we likely won’t get combinations of several drugs combined with radiation in a sequence that we know works, which, like vaccines, may need to be repeated, until we get that specific, memorable response that the body needs to eliminate. Cancer, not just now, but in five years if it recurs.”

The magic of the immune system

Creating this sequence of treatments to help T cells identify and fight cancer cells anywhere in the body is actually similar to the way vaccines work. “The magic of the immune system is not in its strength, but in being specific and having a memory,” says Dr. Hyde. If you think about it, you were vaccinated against polio as a child and had four injections to help your body remember the virus. This is important because if you get polio now, your body will remember this virus. Even if you only have one memory cell left from exposure to the vaccine, that cell will grow into millions of cells and recreate that immune response again. For that we are also working with a combination of radiotherapy and immunotherapy.”

Researchers are now focused on recreating the absolute effect with a specific combination of radiotherapy and immunotherapy drugs designed to provoke an immune attack against cancer throughout the body in a more specific way. Dr. Hyde says clinical trials of treatments offered in different combinations could help scientists determine how to help more patients.