Abstract
BACKGROUND: The complexity and heterogeneity of neutrophils are recognized, especially their roles in modulating inflammation and cancer immune responses. The detailed functions of neutrophils in human tumour-draining lymph nodes (TDLNs), specifically in the context of head and neck cancer, remain inadequately characterized. AIM: This study aims to delineate the phenotypic diversity of neutrophils in TDLNs, non-tumour-draining lymph nodes (nTDLNs) from patients with oral squamous cell carcinoma (OSCC), and to evaluate their correlation with clinical outcomes. METHODS: A flow cytometry-based investigation. RESULTS: Neutrophils manifest a tissue-specific heterogeneity with significant phenotypic differences between compartments. A substantial fraction of neutrophils displayed an activated CD16(high)CD62L(dim) profile in TDLNs, more prominent in patients with advanced T stages, implicating their involvement in the disease's progression. Notably, the presence of this activated neutrophil phenotype in TDLNs was strongly associated with poorer patient prognosis. CONCLUSIONS: The study confirms the heterogeneity of neutrophils in human TDLNs, aligning with findings from animal models but extending them to show clinical relevance in human disease. The correlation of neutrophil phenotypes with cancer progression and prognosis emphasizes the importance of these cells in the tumour-microenvironment. The data suggests a future possibility to develop targeted therapies that modulate the neutrophilic response in OSCC.