Combining Radiation With Immunotherapy May Improve Survival

A Primer on Immunotherapy

The connection between cancer and the immune system was discovered 100 years ago when Dr. William Coley—now known as the father of immunotherapy—saw malignant tumors disappear in patients with cancer who contracted acute streptococcal infections.

Subsequent research sheds light on the strategies cancer cells use to evade detection by the immune system, Quinn said. More recently, new drugs known as checkpoint inhibitors have been developed that address those evasion strategies and enable the immune system to more effectively harness disease-fighting T cells against cancer. To date, however, novel immunotherapeutic agents benefit only a minority of patients and their effectiveness can be short lived.

How Radiation Enhances Immunotherapy

Now evidence is emerging that radiation therapy can not only stimulate immunogenic cell death and sensitize tumor cells to immunotherapy but also cause cells to release tumor antigens that prime T cells to attack other tumor cells at distant sites in the body. This is known as the abscopal effect, or the effect that radiation to one part of the body can have on another, nonirradiated part, Quinn said.

In a trial published in 2017, patients with non-small cell lung cancer who received radiotherapy before treatment with the checkpoint inhibitor pembrolizumab had better progression-free and overall survival than patients who did not receive radiotherapy before pembrolizumab.

Results from preclinical studies suggest that hypofractionated radiotherapy (i.e., larger doses of radiation given over a shorter period of time than standard radiotherapy) generates more tumor-infiltrating T cells and may boost the effectiveness of immunotherapy. In a murine model of mammary carcinoma, treatment with the immunotherapeutic agent ipilimumab alone did not affect tumor growth or survival, but when ipilimumab was combined with hypofractionated high-dose radiation, overall survival significantly improved. Similar results were seen with the combination of ipilimumab and stereotactic radiosurgery.

Effects in CAR T-Cell Therapy

Radiation therapy could have a role to play in broadening the utility of chimeric antigen receptor (CAR) T-cell therapy, in which a patient’s isolated T cells are genetically engineered to express a CAR that recognizes tumor-specific antigens, Quinn explained. When injected back into the patient, the CAR T cells induce cell death.

To date CAR T-cell therapy has been effective only in some types of leukemia and lymphoma. Applying it to solid tumors has proven challenging because of difficulties in target selection. In a recent preclinical study, radiation administered before CAR T-cell therapy rendered tumor cells more susceptible to destruction by the CAR T cells. 

On the Horizon

Looking to the future, biologically guided radiation therapy (Bg-RT) holds great promise, Quinn said. This novel radiation therapy system harnesses molecular signals originating from tumors to guide treatment, personalizing treatment and adapting it to tumor and immune system biology. Bg-RT could offer an efficient approach to the treatment of oligometastases.