A protein identified nearly 40 years ago for its ability to stimulate the production of red blood cells plays a surprising, critical role in dampening the immune system’s response to cancer.

Blocking the activity of the protein turns formerly “cold,” or immune-resistant, liver tumors in mice into “hot” tumors teeming with cancer-fighting immune cells. When combined with an immunotherapy that further activates these immune cells against the cancer, the treatment led to complete regression of existing liver tumors in most mice. Treated animals lived for the duration of the experiment. In contrast, control animals survived only a few weeks.

“This is a fundamental breakthrough in our understanding of how the immune system is turned off and on in cancer,” said the senior author published the work in Science. “I could not be more excited about this discovery, and I hope treatments that target the mechanism we uncovered will quickly move forward to human trials.”