CCR7 Promotes Neutrophil Recruitment and N2 Polarization Through Regulation of IL-16 in Head and Neck Squamous Cell...

While CCR7 is a known driver of head and neck squamous cell carcinoma (HNSCC) progression and tumour-associated neutrophils (TANs) are key microenvironmental mediators, the role of CCR7 in regulating TAN recruitment and pro-tumorigenic N2 polarization remains unknown. This study aimed to delineate this novel regulatory axis.

Bioinformatic analyses of TCGA and HPA datasets were performed to evaluate clinical associations among CCR7 expression, neutrophil infiltration, and N2 polarization markers in HNSCC. Mechanistic insights were obtained from in vitro models using conditioned medium from HNSCC cell lines (FADU, PCI-37B) to study CCR7/IL-16-mediated recruitment and polarization of neutrophil-like HL-60 cells. The functional effects of these N2-polarized neutrophils on HNSCC proliferation and invasion were also quantified.

High CCR7 expression in HNSCC correlated with elevated neutrophil infiltration and N2 polarization markers. CCR7 knockdown suppressed neutrophil recruitment (P < .01) and N2 polarization (P < .001). Mechanistically, CCR7 signalling regulated IL-16 secretion, which mediated neutrophil chemotaxis and N2 polarization (P < .05). These N2-polarized neutrophils promoted a pro-tumorigenic feedback loop, enhancing HNSCC proliferation, migration, and invasion (P < .01).

These findings establish CCR7 as a key regulator of IL-16-mediated neutrophil recruitment and N2 polarization in HNSCC, highlighting its potential as a therapeutic target to remodel the immunosuppressive tumour microenvironment.