Myeloid cells, such as dendritic cells (DCs), macrophages and neutrophils, have been a long-term focus of the lab. Early on we demonstrated the ability of DCs activated ex vivo to induce anti-tumor immunity in patients with cancer. This work led to the development of Sipuleucel-T (Provenge) that was approved by the FDA in 2010 for the treatment of advanced prostate cancer. In 2015, we developed a strategy that reprograms immunosuppressive tumor associated DCs and macrophages into immunostimulatory antigen presenting cells, in situ, that entered clinical trials in 2021.
During the past decade, our research has been directed at understanding the cellular and molecular basis of immune tolerance, which protects us from autoimmune disease but can be “hijacked” by cancers to promote their growth. In cancer, we discovered that lymph node-invading tumor cells induce resident T cells to become tumor specific Tregs that leave the lymph node and migrate to distant sites where they promote metastasis by blocking anti-tumor immunity. We are working now to identify the antigen presenting cells responsible for Treg induction in the lymph nodes. Most recently, we have identified three novel immune checkpoints on myeloid cells. By neutralizing these molecules, we have succeeded in slowing and sometimes eradicating cancers in mice, including metastatic disease. Conversely, stimulating one of these molecules results in immune tolerance that blocks the immune response in an antigen specific manner and can be used to prevent rejection of transplanted organs. These discoveries, which are the basis of current research in the lab, would not have been possible without a collaborative environment in which individual lab members are encouraged to pursue high-risk/high reward ideas and then work with other lab members to test them.
— Dr. Edgar Engleman, Stanford Pathology