Researchers looking to improve immunotherapy for cancer may have succeeded by taking away a tool that tumor cells use to protect themselves.

City of Hope’s Andreas Herrmann, Ph.D., postdoctoral fellow, and Hua Yu, Ph.D., professor, both in the Department of Cancer Immunotherapeutics and Tumor Immunology, focus on a protein called signal transducer and activator of transcription 3, or STAT3. They recently found that blocking STAT3 can help special immune cells to find and attack tumor cells; they reported their findings in Cancer Research online on Sept. 14.

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

The team wanted to see if they could boost the activity of therapeutic T cells. Researchers make therapeutic T cells by genetically engineering a patient’s own normal T cells to recognize and attack cancer cells. City of Hope scientists helped pioneer therapeutic T cells for use against glioma, a deadly form of brain cancer.

“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. When they paired this method with therapeutic T cells to treat lab mice with cancer, 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. Although several drugs that can inhibit STAT3 are available, no current clinical studies using therapeutic T cells include STAT3 suppressors, she said.

The researchers recommend testing some of the STAT3 inhibitors in future T-cell therapy clinical trials.

Other researchers on the current study include Marcin Kortylewski, Ph.D., Maciej Kujawski, Ph.D., Chunyan Zhang, Ph.D., Karen Reckamp, M.D., M.S., Brian Armstrong, Ph.D., Lin Wang, Claudia Kowolik, Ph.D., and Jiehui Deng.

The study was supported by the National Institutes of Health.