Kellie N. Smith, PhD, CRI Lloyd J. Old STAR Johns Hopkins University School of Medicine Area of Research: Lung Cancer Dr. Kellie Smith seeks to decipher how many different types of immune cells cooperate to carry out effective immune responses against tumors.Checkpoint immunotherapy is the standard of care treatment for more than a dozen types of advanced cancer. Unfortunately, while some patients respond, most do not benefit from these treatments, which unleash pre-existing cancer-targeting T cells. Recently, Dr. Smith showed that these immune cells are found even in tumors that don’t respond to checkpoint immunotherapy. Now, her goal now is to characterize these immune cells and understand why they don’t successfully eliminate tumors in lung cancer, even after immunotherapy, with the central aim to understand the full scope of how both “killer” and “helper” T cells contribute to effective anti-tumor immunity. To that end, Dr. Smith developed a novel assay, called MANAFEST, to detect anti-tumor immune responses in patients with resectable and metastatic lung cancer. While conventional approaches study all T cells in the tumor microenvironment in a non-specific way, this approach allows her to specifically study T cells that recognize tumor targets. She is now coupling MANAFEST with other new technologies to define the function and spatial interactions of different types of tumor-targeting T cells before and during checkpoint immunotherapy, with the ultimate aim of discovering new targetable pathways and molecules for combination immunotherapy. Overall, Dr. Smith’s work seeks to apply these technologies to checkpoint immunotherapy-treated tumors and to define key T cell-intrinsic pathways that are important for treatment response and to identify novel targets to overcome immunotherapy resistance. Projects and Grants Exploiting tumor-reactive T cell functional programming for novel therapeutic development Johns Hopkins School of Medicine | Lung cancer | 2023
