Tim Wartewig, PhD, Postdoctoral Fellow Yale University Area of Research: Lymphoma Over the past decade, immunotherapy has become one of the most promising treatments for cancer patients, predominantly due to the revolutionary success of monoclonal antibodies that target the immune checkpoint receptor PD-1 or its major ligand PD-L1. However, the response rate to immune checkpoint therapy is still limited and, dependent on the tumor type, only a subset of the patients responds or shows a stable clinical response. Dr. Wartweig thinks that PD-1 may act as a central gatekeeper of metabolic reprogramming in T-cell mediated anti-tumor immunity as well as in evolution of peripheral T-cell lymphomas (PTCL), which possess a group of highly aggressive hematological cancers for which new treatment regimens are urgently warranted. He hypothesizes PD-1 thereby constitutes a critical barrier to cellular programs of enhanced glycolytic energy supply needed either for T-cell effector functions in the context of immuno-oncology but also for full neoplastic T-cell transformation in lymphomagenesis. His rationale is that the identification and characterization of the PD-1 metabolic gatekeeper mechanism(s) will broaden the knowledge of PD-1 functions in tumor microenvironments, will extend the knowledge on the mechanisms of checkpoint inhibitor therapies, and will also improve understanding of PD-1 tumor suppressor function in T-cell malignancies. The results of this work have the potential to be significant as they will improve therapeutic opportunities in the field of immunooncology and checkpoint inhibitor treatment regimens, and in addition will also provide new treatment rationales for PTCL patients. Projects and Grants Metabolic gatekeeper functions of PD-1 in T-cell anti-tumor immunity and malignant T-cell transformation Yale University | Lymphoma | 2021 | Markus Müschen, MD, PhD
