The Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation at the University of Pennsylvania brings together leading cancer researchers using state-of-the-art molecular, cellular, and radiologic technologies to better understand and optimally modulate signaling pathways activated in cancer and immune cells in patients treated with radiation therapy.

Led by Andy J. Minn, MD, PhD, Associate Professor of Radiation Oncology in Penn’s Perelman School of Medicine, the multidisciplinary center will focus on five highly integrated projects that have multiple synergistic aims. A major goal of the center is the identification of genetic regulators and vulnerabilities associated with the resistance to treatment that arises in cancer as a result of the chronic interferon/anti-viral signaling induced by low doses of radiation over the course of many weeks, which many cancer treatment regimens entail. Toward this aim, scientists in the center will determine whether ultra-high doses of radiation over very short intervals has a different impact on cancer cells, immune cells, and normal tissues compared with conventional radiation doses and intervals, in hopes of designing a regimen with improved efficacy and reduced toxicity.

The team will also examine how persistent interferon/anti-viral signaling suppresses immune cell function and evaluate common regulators shared between cancer cells and immune cells that can be therapeutically targeted. They will seek to understand how modulation of interferon signaling differentially affects individual cancer subclones and immune compartments in heterogeneous tumors. Furthermore, they will engineer CAR T cells to optimize interferon signaling in the tumor microenvironment for maximal tumor killing effects. These studies will provide a deeper understanding of how to genetically, cellularly, and radiologically modulate cancer and immune cells and will accelerate opportunities for physicians to exploit this biology for clinical benefit.

The co-investigators on these projects include:Junwei Shi, PhD; E. John Wherry, PhD; Nancy Zhang, PhD; Jorge Henao-Mejia, MD, PhD; Roger Greenberg, MD, PhD; Sara Cherry, PhD; Constantinos Koumenis, PhD; Igor Brodsky, PhD; and Carl June, MD.