Chen began by discussing that there are two distinct approaches to cancer immunotherapy. The first is enhancement, which he defines as an intervention which enhances normal immune mechanisms. The second approach is normalization, which aims to correct defective immune mechanisms. He compared normalization to unclogging a pipe which is blocked in order to restore the flow of water. Enhancement involves using costimulatory molecules such as cytokines, cancer vaccines, cell therapies, or other immune checkpoint inhibitors to “rev-up” the immune system to treat cancer. He notes that enhancement is problematic in that by enhancing normal immune mechanisms, there can be distinct toxicities
He then discussed approaches to normalize defective immune mechanisms, which is where his discovery of the PD-L1 ligand has been a major breakthrough. PD-L1 on tumor cells can interact with the PD-1 ligand on effector T cells and blocks their mechanism of action which would be to surveil and destroy the tumor cell. In this way, the tumor cells effectively evade the immune system. By blocking the PD-L1 ligand with monoclonal antibodies, the immune system can more effectively surveil and treat tumor cells. As of 2018, his discovery of PD-L1 has lead to 5 FDA-approved drugs for the treatment of solid tumors.
Chen notes that he believes we are at the “end of the beginning” when it comes to our understanding of the role of the immune system in malignancy. He is confident that we will develop biomarkers to determine response to treatment and that we will obtain a better understanding of why some patients have resistance to immunotherapy. He also believes that we may use immunotherapy in the future to treat earlier stage cancers and to treat a wider range of cancers. He notes that immunotherapy is just one of multiple modalities in the treatment of cancer, which we will likely use in combination for maximal efficacy.
Presented by: Lieping Chen, MD, Ph.D. Yale University
Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia PA at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA