Combining EPO inhibition with anti-PD-1 immunotherapy resulted in complete tumor regression in most treated mice, while control mice exhibited significantly shorter survival.

Engleman and colleagues are now focusing on developing therapies that target EPO signaling in human cancers, carefully weighing the risk of anemia against the potential benefits of effective cancer treatment.

This breakthrough suggests a promising avenue for manipulating the immune system in cancer treatment, paving the way for rapid advancement to human trials.

The study involved collaboration with the New York Blood Center and ImmunEdge Inc., where the researchers hold affiliations and positions.

The implications of this research could extend to various solid tumors, warranting further investigation into new therapeutic strategies.

The FDA has previously warned against using EPO in cancer patients due to its association with tumor growth and poor patient prognosis.

A recent study published in *Science* by a team led by Edgar Engleman, MD, Ph.D., reveals a significant breakthrough in understanding cancer immunity, particularly the role of erythropoietin (EPO) in tumor behavior.

The findings indicate that EPO plays a previously unrecognized role in cancer immunity, suggesting that targeting the EPO/EPOR (EPO receptor) signaling pathway could enhance the efficacy of cancer immunotherapies beyond just liver cancer.

Research utilizing preclinical mouse models demonstrated that high levels of EPO are associated with poor prognosis in various cancers, including liver and breast cancers.

The study found that modifying tumor cells to reduce EPO production transformed cold tumors into hot ones, significantly enhancing the immune response.

Future treatments may involve strategies to lower EPO levels or block its receptors on macrophages, despite potential risks such as anemia.

The study also highlighted that combinations of mutations in liver tumors can lead to either immune-privileged cold tumors or inflamed hot tumors that respond to anti-PD-1 immunotherapy.