Yun Ji, Ph.D.

T cell-based immunotherapies have emerged as potent and effective treatments for patients with advanced cancer. Retrospective analyses across multiple clinical trials have revealed that the effectiveness of this type of treatment is critically dependent on the ability of transferred cells to undergo robust proliferation, release high amounts of inflammatory cytokines and persist for long-term. However, the majority of transferred T cells rapidly lose their proliferative and effector capacities following adoptive transfer as they enter into a state of functional exhaustion. Significant efforts have been dedicated to identify approaches to effectively maintain T cell fitness and prevent their exhaustion. We found that CD8+ T cell features can be remarkably improved by genetic manipulation, such as by overexpressing transcription factor Id3 (Ji Y, et al. Nature Immunol, 2011), or by ectopic expression of microRNA miR-155 in tumor-specific CD8+ T cells (Ji Y, et al. Proc Natl Acad Sci U S A, 2015). These proof-of-concept studies suggest that the efficacy of adoptive cell therapy can be greatly improved in a cell-intrinsic manner by regulating the level of transcription factors, microRNAs, or epigenetic modulators essential for T cell fitness. We aim to identify and characterize factors involved in T cell development and differentiation, bearing the goal of translating the results of basic research into clinical trials for cancer patients.