Award: Arthritis and Related Autoimmune Disease Research Grant
Biography: Dr. Apostolidis is currently an Assistant Professor of Medicine at the University of Pennsylvania. His expertise focuses on systemic autoimmunity including rheumatologic immune-related adverse events (irAEs) developing inpatients on cancer immunotherapy. For his work, he combines clinical care of rheumatologic patients with deep immune profiling of their samples to better understand the origins of autoimmunity. Dr. Apostolidis completed a post-doctoral research fellowship at Harvard Medical School working on T cell responses in lupus ,and subsequently a rheumatology fellowship at the University of Pennsylvania in Dr .Wherry’s lab studying irAEs. As of July 2024, he has established a translational immunology laboratory at the University of Pennsylvania focused on understanding the fundamental mechanisms of irAEs in cancer immunotherapy. Dr. Apostolidis leads a vibrant team of researchers combining clinical insights with innovative immunological techniques to develop novel approaches for managing autoimmune complications while preserving anti-tumor responses in immunotherapy patients. His lab serves as a bridge between rheumatology and oncology, working to improve outcomes for patients in both specialties.
Research Summary: Immune-related adverse events (irAEs) occur in about 40% of patients receiving cancer immunotherapies and can significantly disrupt treatment
Among these, rheumatologic irAEs cause severe joint and muscle pain; in nearly one-third of cases, they persist long after therapy ends. These autoimmune complications share similarities with classic rheumatic diseases such as rheumatoid arthritis, suggesting that similar immune pathways may drive both conditions.
Our study focuses on a specific population of immune cells called IL-7R+ CD8 Tcells. Wehave observed that patients who develop rheumatologic irAEs tend tohave higher levels of these cells before starting treatment. After immunotherapy,these IL-7R+ CD8 T cells are more prone to becoming “autoreactive”, which makesthem capable of damaginghealthy tissues. In addition, our genetic analyses showthat these cells may carry harmful mutations, contributing to their heighteneddisease-causing potential.
To investigate these findings, we will analyze blood samples from a large group of cancer patients undergoing immunotherapy, using cutting-edge techniques to detect gene mutations and measure how these T cells respond to signals that activate or suppress them. By pinpointing the factors that trigger IL-7R+ CD8 T cells to cause rheumatologic irAEs, we aim to develop new ways to prevent and treat them.
Ultimately, we hope our research will enable patients to continue life saving immunotherapies without suffering long-lasting autoimmune complications. At the same time, uncovering these immune pathways may benefit individuals with established primary rheumatologic diseases, providing broader knowledge into the biology of autoimmunity
