Provided herein are methods of manipulating ARID5B expression in immune cells such NK cells, T cells, and T cell and NK cell progenitors to enhance their persistence and function in vivo. Also provided herein are modified immune cells and compositions comprising such modified cells for anti-cancer, anti-viral, and other immunotherapies. In some embodiments, immune cells are genetically modified to increase ARID5B expression and, thus, improve persistence, increase in vivo anti-tumor efficacy, and increase viability and functionality of the modified cells after freezing and thawing.