Cancer is crafty. It can protect itself from the immune system, which normally would make short work of tumor cells. This ability poses problems for researchers aiming to use immunotherapy to defeat the disease.

But scientists may have found a weakness in cancer’s anti-immunotherapy armor.

Andreas Herrmann found that blocking STAT3 helped therapeutic T cells fight cancer. (Photo by Darrin S. Joy)

Andreas Herrmann, Ph.D., postdoctoral fellow, and Hua Yu, Ph.D., professor, both in City of Hope’s Department of Cancer Immunotherapeutics and Tumor Immunology, focus much of their research on a protein called signal transducer and activator of transcription 3, or STAT3. They recently found that blocking STAT3 might help revved-up, cancer-fighting T cells work better.

T cells are white blood cells that normally protect the body from disease.

Researchers design therapeutic T cells to fight tumor cells. They genetically engineer a patient’s own normal T cells to specifically recognize and attack cancer cells.

“T-cell therapies are very promising, but clinical researchers using engineered T cells to fight cancer have had mixed results,” Herrmann said. “That’s at least partly because immune response is suppressed in cancer patients.”

Scientists know that tumor cells use STAT3 to hide and protect themselves from the body’s defenses, so the research team looked for ways to block it.

They created a new method that prevents key immune system cells from making STAT3. And when they paired this method with therapeutic T cells, they found the T cells became much better at destroying cancer cells.

The finding is an important step toward boosting the potential of T-cell therapies to fight cancer in humans.

“These experiments show that suppressing STAT3 activity might help patients,” Yu said. Several available drugs can inhibit STAT3, but no current clinical studies using therapeutic T cells include STAT3 blockers, she said.

The researchers recommended that future T-cell therapy clinical trials also include STAT3 inhibitors to see if they boost the therapy’s benefit.