Decoding the Metabolic-immune Axis: Neutrophil glycolysis-driven tumor niche remodeling and its therapeutic exploitation.

Neutrophils are an important component of the tumor microenvironment, with the majority of previous research concentrating on their anti-tumor role. Recent research indicates that elevated neutrophil-lymphocyte ratios are indicative of worse cancer prognoses. In addition, it revealed the functional transition of neutrophils are related with metabolic regulation within the tumor microenvironment.The metabolic-immune axis has emerged as a master regulator of tumor progression, yet the role of neutrophil-centric crosstalk in this paradigm remains enigmatic. Therefore, this study highlights the innovative role of neutrophils in tumorigenesis, particularly the regulatory effect on tumor niche transformation after glucose metabolism reprogramming. Simultaneously, we discussed how the tumor microenvironment alters the glucose metabolism of neutrophils, influences their life cycle, and modifies their localization and activity inside the tumor niche. In addition, targeted neutrophils, including new therapies in clinical trials, offer new possibilities for cancer treatment. This work establishes neutrophil glycolysis as a linchpin of the metabolic-immune ecosystem and provides a combinatorial therapeutic blueprint to dismantle pro-tumorigenic niches.