Abstract: Described herein are methods for activating or differentiating a T cell comprising contacting a T cell with a pharmaceutically effective amount of an agent that inhibits Yap and culturing the T cells for a time, and under conditions sufficient to induce activation or differentiation. Compositions comprising the activated or differentiated T cells, and methods for treating a disease or disorder caused by or associated with T cell dysfunction comprising administering the same are described herein. In one embodiment, the disease or disorder is cancer, an autoimmune disease or a microbial infectious disease.