Uncoupling Therapeutic Efficacy from Immune-Related Adverse Events in Immune Checkpoint Blockade
Weilei Hu,
Guosheng Wang,
Yian Wang,
Matthew J. Riese,
Ming You
Affiliations
Weilei Hu
Center for Disease Prevention Research and Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Guosheng Wang
Department of Biomedical Engineering, Binghamton University—SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA
Yian Wang
Center for Disease Prevention Research and Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Matthew J. Riese
Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Blood Research Institute, Versiti Inc, Milwaukee, WI 53226, USA
Ming You
Center for Disease Prevention Research and Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; Corresponding author
Summary: Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.