Abstract:
Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As
immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase
9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factorrelated
apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their
involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer
effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such
as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells.
Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor,
intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide
neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing
the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophilmediated
support or inhibition of tumor progression, with a particular focus on elucidating the internal and external
factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding
the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil
research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies
targeting neutrophils.
