Radiation therapy, the immune system and what lies ahead

Radiation therapy is often considered a treatment for localized cancer that has not spread. However, when combined with other therapies, it may be an effective option for patients with metastatic disease.

“It has long been known that there are ways to use drugs to make radiation therapy even more effective,” says Benjamin Schrank, MD, Ph.D., radiation oncology resident and member of the Wen Jiang Laboratory. Established examples include cisplatin for patients with head and neck or gynecologic cancers, 5-fluorouracil for patients with gastrointestinal cancer, and temozolomide for patients with glioblastoma.

New research presented by Schrank at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting offers a new avenue for immunotherapy-based cancer treatment.

“We go beyond the idea of ​​radiation as a local therapy and assume that radiation can trigger an immune response that can then work with other types of drugs to treat cancer,” says Schrank.

Radiation therapy combinations help exploit DNA damage

A chemotherapy drug such as a cytotoxic drug works well with radiation therapy because the radiation damages the DNA of cancer cells, weakening them. Both therapies cause DNA damage, so the effect is increased when used together.

“We tip the scales so much that the cancer cells cannot survive,” says Schrank.

In some situations, radiation therapy can further exploit the unique properties of cancer cells, such as DNA repair mutations. “We are able to take advantage of these specific tumor mutations and use radiation and a drug to target DNA repair more effectively,” says Schrank. This is seen in certain glioblastoma patients when DNA repair mutations are treated with radiation therapy and temozolomide.

The immune-activating potential of radiotherapy

However, the benefits of these combinations are not just due to the drugs that are combined with radiation therapy. “Several studies in both preclinical and clinical settings have shown that radiotherapy can modulate the immune response. When used correctly, it can actually improve the immunogenicity of tumors and allow the immune system to better recognize tumor cells,” says Wen Jiang, MD, Ph .D.

Radiation can trigger immune signals that can trigger a systemic antitumor response. “We have increasingly recognized that radiation itself is almost like a drug. When administered in very high doses, it becomes immunogenic,” says Schrank.

This advantage has been studied and further developed by researchers M.D. Anderson in several types of cancer, including lung cancer, when stereotactic body radiation therapy is combined with immunotherapy.

“We are actively studying how tumors respond to radiation and immunotherapy to make the benefits of combination therapy a reality for every patient,” says Schrank.

Antibody-drug conjugate intended to trigger an immune response

While radiation can stimulate the immune system, Schrank's recent research into a first-in-class antibody-drug conjugate (ADC) offers a complementary immune-driven strategy. This work will be presented at the 2024 Annual Meeting of the American Society for Radiation Oncology.