Increased tumor-infiltrating plasmacytoid dendritic cells promote cancer cell proliferation and invasion via TNF-α/NF-κB/CXCR-4 pathway in oral squamous cell carcinoma.

Tumor-infiltrating immune cells are closely associated with tumor occurrence and progression. The present study explored the potential mechanism of tumor-infiltrating plasmacytoid dendritic cells (pDC) mediating the proliferation and metastasis of cancer cells in oral squamous cell carcinoma (OSCC). pDC distribution was detected by immunofluorescence and flow cytometry. chemotaxis cytokine receptor-4/7 (CXCR-4/7) expression was detected by quantitative polymerase chain reaction and immunohistochemistry. Cell proliferation and migration were measured by CCK-8, colony formation, wound healing and transwell assay. ELISA and western blotting were used to investigate cytokines secretion and NF-κB pathway activity. Tumor-infiltrating pDC in OSCC was significantly increased and associated with tumor size, lymph node (LN) metastasis ( <0.05). Tumor-infiltrating-pDC-conditioned medium from OSCC patients significantly promoted tumor cell proliferation and invasion, which was at least partly mediated via enhancing the CXCR-4 expression of tumor cell. In addition, the activation of NF-κB pathway played a decisive role in the overexpression of CXCR-4, which was further regulated by pDC-derived TNF-α secretion. Tumor-infiltrating pDC promoted oral cancer proliferation and invasion via activating the TNF-α/NF-κB/CXCR-4 pathway, which may serve as a potential immunological target for the treatment of OSCC in the future.