Described herein are novel compositions comprising IL-27 or NFIL-3 modulators (i.e., inhibitors or activators), and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, and modulating TIM-3 activity or expression. These compositions, methods, and uses are useful for the treatment of chronic immune conditions, such as persistent infections, cancer, and autoimmune diseases.
