Targeting glutamine metabolism crosstalk with tumor immune response

Abstract

Glutamine, akin to glucose, is a fundamental nutrient for human physiology. Tumor progression is often accompanied by elevated glutamine consumption, resulting in a disrupted nutritional balance and metabolic reprogramming within the tumor microenvironment. Furthermore, immune cells, which depend on glutamine for metabolic support, may experience functional impairments and dysregulation. Although the role of glutamine in tumors has been extensively studied, the specific impact of glutamine competition on immune responses, as well as the precise cellular alterations within immune cells, remains incompletely understood. In this review, we summarize the consequences of glutamine deprivation induced by tumor-driven glutamine uptake on immune cells, assessing the underlying mechanisms from the perspective of various components of the immune microenvironment. Additionally, we discuss the potential synergistic effects of glutamine supplementation and immunotherapy, offering insights into future research directions. This review provides compelling evidence for the integration of glutamine metabolism and immunotherapy as a promising strategy in cancer therapy.