Enhancement of effector CD8 T cell motility by IL-21 through STAT3 4131

Abstract Description CD8 T cells are a critical component of the immune response to infections as well as in prevention and restriction of cancer growth. Across multiple solid cancer types, tumor infiltration of CD8 T cells is associated with improved patient survival. CD8 T cell cytotoxicity and cytokine production have been characterized as the primary mechanisms by which these cells execute their immune function. However, basal cell motility, defined as random walk and exploratory spread, is an essential and underappreciated aspect of the CD8 T cell-mediated antitumor response. Cell motility enables effector CD8 T cells to search for and reach their cell targets within a solid tumor microenvironment. Here, we investigate the impact of IL-21 on effector CD8 T cell motility. We show that compared to effector CD8 T cells expanded in the presence of IL-2 alone, those expanded in IL-2 and IL-21 exhibit increased cell motility in vitro and in vivo. We also show that IL-21 enhances mitochondrial respiration and mitochondrial calcium in effector CD8 T cells. Our data suggests that increased mitochondrial calcium and mitochondrial ATP promote CD8 T cell motility through IL-21-mediated STAT3 activity. Therefore, IL-21 plays an important role in effector CD8 T cell mitochondrial fitness, cytoskeleton stiffness, and cell motility, which can be leveraged in the design of adoptive T cell therapies for the treatment of solid tumors. Funding Sources Supported by NIH R01 CA260909; T32AI007405. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)