Tumor cells-derived CXCL17 is associated with up-regulated neutrophil to monocyte ratio and predicts poor prognosis in oral squamous cell carcinoma

CXCL17, the most recently identified member of the chemokine family, has been implicated in angiogenesis, tumorigenesis, infection, and inflammation across various tumors. However, the expression profile and functional characterization of CXCL17 in oral squamous cell carcinoma (OSCC) remain inadequately explored. Based on our previous proteomics studies of OSCC patients, we reported the elevated CXCL17 expression in tumor tissues compared to adjacent non-tumor tissues. We originally characterized the prognostic value of CXCL17 and its spatial and temporal distribution in 72 OSCC tissue specimens by immunohistochemistry staining. Elevated CXCL17 expression was correlated with advanced tumor stage, increased distant metastasis, and significantly shorter overall survival. Multivariate analysis confirmed tumor cell–derived CXCL17 as an independent prognostic factor for overall survival. Additionally, we investigated the relationship between CXCL17 and peripheral blood indicators hypothesizing that CXCL17 may influence peripheral immune cell regulation. We revealed that higher CXCL17 in tumor center was associated with reduced postoperative neutrophil, preoperative monocyte and postoperative leukocyte. Moreover, CXCL17 levels in tumor center was correlated significantly with preoperative neutrophil-to-lymphocyte ratio (NLR) and postoperative lymphocyte-to-monocyte ratio (LMR). Elevated postoperative neutrophil-to-monocyte ratio (NMR) was associated with advanced TNM stage and higher lymph node metastasis rates, and was also observed in patients with postoperative distant metastasis. In summary, these findings suggest that CXCL17 contributes to OSCC progression and poor prognosis by modulating systemic immune responses and reshaping the tumor immune microenvironment, highlighting its potential as both a prognostic biomarker and a therapeutic target.