A team led by researchers at the University of Freiburg has found how some blood cancers known as myeloproliferative neoplasms (MPNs) bypass the immune system. The work was published yesterday in Science Translational Medicine.
Some cancers have been found to overtake the PD-1/PD-L1 pathway to prevent T cells from attacking malignant cells. However, scientists were unsure if MPNs, a blood cancer where bone marrow makes too many red blood cells, white blood cells or platelets, avoided the immune system through similar trickery.
Alessandro Prestipino, coauthor of the paper, and the team has found that many people with MPNs have abnormally activated versions of a signaling protein named JAK2, a molecule that helps activate PD-L1 production.
An anti-PD-1 checkpoint inhibitor was given to a patient with MPN polycythemia vera who had undergone a stem cell transplant and subsequently relapsed. With the inhibitor, the patient experienced improved symptoms. The anti-PD-1 therapy was also effective in mice with MPNs.
When T cells from healthy donors were grown in culture with JAK2-mutant cells, the T cells turned down gene expression for growth and energy production. According to the researchers, this result is consistent with the observation that mutant JAK2 drives immune cell exhaustion. The team has also looked closer for the specific proteins that work with mutant JAK2 to boost PD-L1. The authors believe that more types of cancer may also be driven by other cancer-driving mutations that cooperate with similar immune-escape mechanisms.