How to reinvigorate exhausted immune cells to stop cancer

The human immune system relies on a delicate balance of finely tuned cell types that keep germs and cancerous cells in check. In cancer and chronic infections, this balance can be disrupted, resulting in immune system dysfunction or “exhaustion.” An important protein called TOX, which varies in amount in different immune cell types, controls the identity of the cells that become exhausted, according to researchers in the Perelman School of Medicine

Tox protein in DNA
Exhausted CD8 T-cell with TOX functioning in the nucleus. (Image: John Wherry, Penn Medicine)

With this knowledge, investigators now have a way to accurately identify immune cells that are exhausted in a tumor or site of an infection, which could allow clinicians to improve the effectiveness of patients’ immune response to cancer treatments by reinvigorating exhausted T-cells. This work is published in Nature.

“The discovery of TOX as the key regulator of exhausted T-cells now allows us to envision immunotherapies that target, or engineer, TOX to reverse or prevent exhaustion and improve immunity to infections or cancer,” says senior author E. John Wherry, chair of the department of Pharmacology and director of the Penn Institute of Immunology.

Read more at Penn Medicine News.