In conclusion, our data provide strong evidence that impaired tumor-infiltrating pDC are a strong predictor for LN metastasis in oral cancer, and that increased tumor-infiltrating pDC contributes to upregulation of CXCR-4 expression, possibly through TNF-α-mediated NF-κB activation, which ultimately leads to cell proliferation and migration toward LN via the CXCR4/SDF-1 chemoattraction axis. Here, CXCR4 is linked to lip and oral cavity carcinoma.