A new study has shown that radiation therapy can make certain lung cancers more responsive to immunotherapy, even if they usually don’t respond to such treatments.
This discovery could lead to better outcomes for many patients with hard-to-treat lung cancers.
The research was led by teams from the Johns Hopkins Kimmel Cancer Center and the Netherlands Cancer Institute and was published in Nature Cancer.
Immunotherapy helps the body’s immune system find and attack cancer cells. It works well in some cancers, but not all. Some tumors, known as “cold” tumors, don’t attract immune cells and are often resistant to immunotherapy.
These include tumors with certain biological markers like low mutation counts, low PD-L1 protein levels, or mutations in a signaling pathway called Wnt.
Radiation therapy, which is usually used to kill cancer cells at a specific site, has a unique effect called the abscopal effect. This happens when radiation to one tumor site leads to immune responses throughout the body.
The idea is that when radiation kills cancer cells, it releases tumor material into the area, which helps the immune system recognize the cancer and attack it more effectively—even at distant sites that weren’t treated directly.
To understand this effect better, researchers studied 72 patients with non-small cell lung cancer. Some received immunotherapy alone, while others received radiation therapy followed by immunotherapy.
The researchers collected nearly 300 blood and tissue samples before and after treatment and studied them using various scientific tools to track how the immune system was reacting.
They found that tumors far away from the radiation site began to show signs of immune activity after the combined treatment. In other words, the “cold” tumors were “warming up,” showing more immune cell activity and attracting more T cells—the immune system’s fighter cells. This shift was linked to better treatment results.
The team confirmed that the T cells expanding in the body after combined treatment were actively recognizing specific tumor mutations. Patients with cold tumors who had this immune response tended to live longer than those who received only immunotherapy.
This is important because it suggests that radiation therapy could be used to “prime” the immune system in patients whose cancers usually don’t respond to immunotherapy. It opens new possibilities for patients who previously had limited treatment options.
The study is part of a clinical trial conducted in partnership with Dutch researchers and was supported by the National Institutes of Health and other cancer research groups. It also shows how combining efforts across countries and scientific disciplines can lead to discoveries that improve cancer care.
The research team continues to study how to measure immune responses more accurately using tumor DNA found in blood. These efforts may help doctors better track treatment success and personalize care in the future.
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The study is published in Nature Cancer.
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