Dr. Engleman’s research is directed at understanding the role of immune cells in health and disease. Early in his career, he generated monoclonal antibodies to human T lymphocytes, including CD4 and CD8, enabling investigators worldwide to study these cells. He used the antibodies to analyze the mechanism and consequences of HIV infection and then transitioned to studies of the immune system in cancer. He demonstrated that antigen-loaded dendritic cells (DCs) can induce anti-tumor immunity in cancer patients, leading to the development of Sipuleucel-T (Provenge), the first FDA-approved cell therapy. Recently, his research has focused on understanding the mechanism responsible for peripheral immune tolerance.  His group discovered that erythropoietin (EPO) dictates such tolerance by interacting with EPO receptors (EPOR) on cDC1s, causing these cells to become tolerogenic through their induction of antigen-specific Tregs and suppression of cytotoxic CD8 T cells. This pathway plays a critical role in maternal-fetal tolerance as well as radiation-induced transplant tolerance, but it is also activated in some cancers and infections.  In mice, removal or blockade of EPO or EPOR reverses tolerance in cancer and results in tumor regression, while enhanced EPOR signaling promotes tolerance to organ transplants, pointing the way to new treatments for a variety of diseases.