• Posted July 28, 2025

Autoantibodies Influence Cancer Response To Immunotherapy, Study Says

Cutting-edge immunotherapy drugs are incredibly effective against some cancers but barely put a dent in others – and researchers might now know why.

Patients’ own autoantibodies – immune proteins traditionally associated with autoimmune diseases like psoriasis and lupus – appear to dramatically influence their individual response to immunotherapies, researchers report in the journal Nature.

“Our analysis shows that certain naturally occurring autoantibodies can tilt the odds dramatically toward shrinking tumors,” senior researcher Dr. Aaron Ring, chair of immunotherapy at Fred Hutchinson Cancer Center in Seattle, said in a news release.

“We saw some cases where autoantibodies boosted a patient’s likelihood of responding to checkpoint blockade by as much as five- to ten-fold,” he said.

The study focused on immune checkpoint inhibitors, drugs that boost the body’s ability to attack on cancer by removing cancer cells’ ability to evade detection by the immune system.

These drugs have transformed treatment for a wide range of cancers, including melanoma and certain types of lung cancer, researchers said in background notes. However, not all patients respond to the medications.

Researchers screened for more than 6,000 types of autoantibodies in blood samples taken from 374 cancer patients receiving checkpoint inhibitors and 131 healthy people.

“For years, autoantibodies were viewed mainly as bad actors in autoimmune disease, but we’re discovering they can also act as potent, built-in therapeutics,” Ring said. “My lab is mapping this hidden pharmacology so we can turn these natural molecules into new treatments for cancer and other illnesses.”

Results showed that cancer patients had substantially higher levels of autoantibodies compared to healthy folks.

Importantly, certain autoantibodies were linked to better outcomes among cancer patients, researchers said.

For example, autoantibodies that blocked an immune signal called interferon were linked to better tumor attacks  by checkpoint inhibitors.

This finding mirrors other studies, which have found that too much interferon can exhaust the immune system, limiting the effects of immunotherapy, researchers said.

“In some patients, their immune system essentially brewed its own companion drug,” Ring said. “Their autoantibodies neutralized interferon and that amplified the effect of checkpoint blockade. This finding gives us a clear blueprint for combination therapies that intentionally modulate the interferon pathway for everyone else.”

However, not all autoantibodies helped cancer patients. Several were associated with worse outcomes, likely because they disrupted critical immune system pathways necessary to combat cancer, researchers said.

Finding ways to eliminate or counteract those autoantibodies might improve the effectiveness of immunotherapy in patients who otherwise might not benefit, researchers said.

“This is only the beginning,” Ring said. “We’re now extending the search to other cancers and treatments so we can harness — or bypass — autoantibodies to make immunotherapy work for far more patients.”

More information

The National Cancer Institute has more on immunotherapy for cancer.

SOURCES: Fred Hutchinson Cancer Center, news release, July 23, 2025; Nature, July 23, 2025