Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy

Abstract

Immune cell metabolism plays a pivotal role in regulating cellular proliferation, differentiation, and functional responses, collectively shaping immune responses within the tumor microenvironment (TME). Recent advancements increasingly highlight diverse metabolic phenotypes of immune cells and their complex interplay with tumor dynamics. Immune cell metabolism exhibits remarkable plasticity, enabling metabolic networks to finely tune immune cell behaviors in response to external stimuli. Furthermore, a strong correlation between metabolic profiles and immune cell fate, activation, and function has been repeatedly delineated in immunometabolism. Consequently, targeting the metabolic networks, referred to as metabolic checkpoints, to reprogram immune cell phenotypes and bolster antitumor immunity holds significant promise for clinical translation. This review summarizes the latest developments in multifaceted metabolic checkpoints, with a focus on how metabolic checkpoints modulate immunological consequences and cancer progression. Lastly, potential strategies for targeting metabolic checkpoints are explored to inspire innovative approaches in immunotherapy.