Figure 7.

The hybrid engine model: an updated view of the molecular machinery that powers antitumor T cell immunity. (A) Nutrients that serve as the biofuels, which can be limiting in the tumor microenvironment. (B) The hybrid engine model. To analogize the hybrid car, a tumor-targeting CD8 T cell utilizes a “molecular fuel engine,” such as aerobic glycolysis and/or tricarboxylic acid cycle, to convert nutrients/biofuels into bioenergy in the form of ATP, while using creatine as a “molecular battery” to store bioenergy and buffer the intracellular ATP level to power T cell antitumor activities. (C) Creatine can be obtained from creatine-rich dietary resources, mainly red meat, poultry, and fish, as well as from dietary supplements. (D) However, the best cancer therapy benefits would come from clinical intervention by administering creatine to cancer patients following specially designed dosing strategies.