Safe To Use Both

Immunotherapy drugs are revolutionizing the treatment of many cancer types, but not all patients treated with these new drugs respond. To enhance the efficacy of immunotherapy, researchers at The University of Texas MD Anderson Cancer Center are exploiting a rare phenomenon of radiation therapy in clinical trials for patients with lung cancer and other solid malignancies.
                                                             

“Radiation has been used for a hundred years to do one thing: achieve local control,” said James Welsh, M.D., an associate professor in the Department of Radiation Oncology. “We are now combining it with immunotherapy for systemic control, and that’s pretty exciting.”

Seeking synergy
Alone, drugs that inhibit immune checkpoints—CTLA-4 (cytotoxic
T lymphocyte antigen 4), PD-1 (programmed cell death protein 1), or PD-L1 (the PD-1 ligand)—can elicit impressive responses in some cancer patients, even in those with metastatic disease. However, immunotherapy eliminates distant disease in perhaps only 20% of patients with metastatic cancer; Dr. Welsh hopes to use radiation to push that rate to 30% or even 40%.
                                                                  

At first glance, the logic of combining radiation therapy with immunotherapy to fight cancer seems obvious. Radiation, which kills cancer cells by damaging their DNA, is given locally; immunotherapy is given to ramp up the immune system to attack the disease systemically. But this is only a partial explanation of how the combination might assault the disease. Rather than one treatment providing just local disease control and the other providing just systemic control, the therapies may work synergistically. One area of synergy is that radiation can stimulate immunogenic cell death and sensitize cancer cells to immunotherapy by promoting the expression of major histocompatibility complex (MHC) class I molecules and other apoptosis-mediating proteins.

“We developed a model of resistance to PD-1 inhibition in my lab. Tumor cells lose the expression of MHC class I molecules, which present antigens to cytotoxic T cells,” Dr. Welsh said. “Radiation can make tumor cells express those molecules and respond to immunotherapy. We’ve shown that in mice and a few humans so far.”

In addition to sensitizing irradiated tumor cells to immunotherapy, radiation can cause the cells to release tumor antigens that prime T cells to attack other tumor cells in the body, including those at distant, non-irradiated sites.

“Effectively, radiation can turn the tumor into a vaccine,” Dr. Welsh said.