Cytotoxic T lymphocytes are our most important defense against tumors or virus-infected cells. Recent advances in understanding T cell biology led to breakthrough discoveries for treating cancer or chronic virus infections. Despite the unprecedented success of T cell immunotherapy in treating multiple previously refractory cancers, many patients remain nonresponsive, while other patients relapse after initial clinical response. We are interested in elucidating the molecular mechanisms that regulate cytotoxic CD8 T cell function and response to immunotherapies.