Mechanisms and Targeting Strategies of Neutrophils Promoting the Release of Dormancy from Disseminated Tumor Cells in the Lung

The lung is a frequent site of secondary metastasis for various cancers, not only due to its extensive vasculature and lymphatic network but also because its immune microenvironment is highly susceptible to inflammatory modulation by external insults such as smoking, aging, infection, or chemotherapy. Recent evidence indicates that neutrophils play a pivotal role in this process. Upon activation by chronic inflammation and tumor-derived factors, neutrophils form neutrophil extracellular traps (NETs) and release a wide range of inflammatory mediators, which remodel the extracellular matrix (ECM) and activate signaling pathways, collectively disrupting the dormancy-maintaining niche and triggering disseminated tumor cells (DTCs) proliferation. Moreover, neutrophils cooperate with immunosuppressive stromal and immune components to establish a permissive microenvironment that facilitates DTC immune evasion and reactivation. These insights redefine neutrophils as key “dormancy releasers” rather than passive bystanders in tumor progression. Understanding the molecular and cellular mechanisms underlying neutrophil-induced dormancy escape offers novel therapeutic opportunities for preventing metastatic recurrence in the lung.