Snail1 retains CD8+T cell effector function in tumor immunity 2104

Abstract Description While cancer cells adapt to the tumor environment by maintaining a low level of differentiation despite high proliferation, T lymphocytes undergo terminal differentiation. One of the unique adaptive mechanisms in tumors is the epithelial-to-mesenchymal transition (EMT). We identified that the EMT gene Snail1 may also be expressed by effector CD8+ T cells, and IL-2 maintains its expression via STAT5 and GSK-3. Snail1 enhances T cell persistence and stabilizes their effector phase by enhancing the β-catenin pathway. Snail1 expression in CD8+ T cells is associated with increased anti-tumor immunity in animal models and correlates with the efficacy of immune checkpoint blockade in cancer patients. Treatment with H9T, an engineered IL-2 partial agonist, enhances Snail1-dependent T cell immunity in vivo. Snail1-expressing CAR-T cells show superior persistence and anti-tumor activity in preclinical models. Thus, Snail1 is a potential target for cancer immunotherapy. Funding Sources CA248430 Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)