E. John Wherry, PhD
The American Association for Cancer Research (AACR) awarded E. John Wherry, PhD, with the 2023 AACR–Cancer Research Institute Lloyd J. Old Award in Cancer Immunology during the AACR Annual Meeting in April in Orlando, Florida.
Dr. Wherry is Chair of the Department of Systems Pharmacology and Translational Therapeutics, Director of the Institute for Immunology, and founding Director of the Immune Health Project in the Perelman School of Medicine at the University of Pennsylvania. He is being honored for his major fundamental discoveries associated with deciphering the mechanisms of T-cell exhaustion in cancer, which has aided and informed research dedicated to establishing effective checkpoint blockade immunotherapies and has revealed novel approaches to reinvigorate T cells.
Dr. Wherry is internationally recognized for his groundbreaking achievements in basic, translational, and clinical immunology, influencing the scientific understanding of cancer immunobiology and immunotherapy. His work has defined the concept of T-cell exhaustion and has distinguished exhaustion from other types of immune system nonresponsiveness. Dr. Wherry was instrumental in first identifying PD-1 expression by exhausted T cells and in characterizing the co-regulation of exhaustion by PD-1 and other inhibitory receptors. His innovative research has laid the foundation for demonstrating that exhausted T cells are a critical target of PD-1 checkpoint blockade in cancer. This treatment has transformed many previously intractable cancers into chronic diseases.
Recently, Dr. Wherry has discovered new developmental biology pathways governing the lineage dynamics of exhausted T cells. His laboratory team is now attempting to identify and catalog associated signals that control cellular homeostasis. Further, Dr. Wherry and his team at Penn Medicine’s Abramson Cancer Center are working to develop new cellular engineering techniques to generate cell-based therapies, such as chimeric antigen receptor T cells, by targeting noncoding genomic regulatory elements that control state-specific gene regulation in exhausted T cells. More recently, Dr. Wherry’s group has pioneered deep immune profiling pipelines that allow an “immune health” fingerprint to be defined and monitored over time. This approach is being explored in patients with cancer and individuals affected by COVID-19 to study clinical perturbations whereby alterations in an individual’s immune health profile may subsequently help determine current and future immune competency.
Awards and Training
Dr. Wherry has received numerous awards and honors throughout his career, including the International Society for Advancement of Cytometry CYTO Hooke Award (2022), the University of Pennsylvania Perelman School of Medicine Stanley N. Cohen Biomedical Research Award (2021), the Stand Up To Cancer Sharp Award (2018), and the CRI Frederick W. Alt Award for New Discoveries in Immunology (2016). He is an elected Fellow of the American Association for the Advancement of Science (2022).
Dr. Wherry received his undergraduate degree from Pennsylvania State University and his PhD in immunology at Thomas Jefferson University. He completed a postdoctoral fellowship with Rafi Ahmed, PhD, at Emory University.