Provided herein is a method of treating cancer and stimulating anti-tumor immunity in a subject in need thereof, the method including administering to the subject a synergistic, therapeutically effective amount of a PFKFB3 inhibitor, such as PFK-158, in combination with an immune checkpoint inhibitor. Also provided is a method of synergistically increasing activity of an immune checkpoint inhibitor, the method including administering to a subject in need thereof a combination therapy including PFK-158 and the immune checkpoint inhibitor. A pharmaceutical composition including PFK-158, at least one immune checkpoint inhibitor； and at least one pharmaceutically-acceptable carrier is also provided.
