Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment

The increased glutamine demand of malignant cells imposes profound metabolic pressure on immune cells, particularly macrophages, forcing adaptive changes in their glutamine utilization pathways. This metabolic reprogramming involves three interconnected processes, namely, glutamine biosynthesis, catabolic breakdown, and cellular uptake, which are precisely regulated by specialized enzymes, metabolic intermediates, and membrane transport systems. As a pivotal area in modern oncology, glutamine metabolism serves as a master regulator of macrophage biology, simultaneously governing their bioenergetic requirements and immunological competence, thereby critically influencing tumor progression and metastatic potential. Our examination further reveals the intricate involvement of glutamine metabolic pathways in shaping the immunosuppressive tumor microenvironment and their dynamic interactions with host anti-tumor immune responses. These insights illuminate the therapeutic potential of targeting glutamine metabolism as an innovative strategy to improve cancer treatment paradigms.