Increased tumor-infiltrating plasmacytoid dendritic cells predicts poor prognosis in oral squamous cell carcinoma.

OBJECTIVE: Accumulating evidence suggests that plasmacytoid dendritic cells (pDC) have a dual role not only in initiating anti-tumor immune responses but also in inducing immune tolerance to facilitate cancer development. The aim of this study was to investigate the distribution and function of tumor-infiltrating pDCs in primary oral squamous cell carcinoma (OSCC) and their relation to patient outcome.

METHODS: The distribution of pDCs in 10 normal oral mucosa and 60 OSCC tissues was detected by immunohistochemistry. The population of pDCs in six OSCC patients and six healthy donors was evaluated by flow cytometry. The relationship between tumor-infiltrating pDCs and clinicopathological data and patient outcome was analyzed accordingly. The capacity of pDCs to produce cytokines, such as IFN-α, IL-6, IL-8 and TNF-α in response to TLR-9 ligands (CpG-ODN) was measured by ELISA.

RESULT: PDCs were detected at high levels in 38.3% of the OSCC tissues, primarily in the stroma, but were absent in normal oral mucosa. The frequency of pDCs in OSCC tissue was significantly higher than that observed in normal oral mucosa. However, the distribution and population of circulating pDCs was similar between healthy donors and OSCC patients. Kaplan-Meier analysis revealed a significant association of increasing number of tumor-infiltrating pDCs with lymph node metastasis and overall survival. Multivariate analysis confirmed that high levels of tumor-infiltrating pDCs was an independent prognostic factor. Further cytokine analysis revealed a decreased secretion of IFN-α, IL-6 and TNF-α, which indicated an impaired function of tumor-infiltrating pDCs.

CONCLUSIONS: The increased number of tumor-infiltrating pDCs correlates with an adverse outcome in primary OSCC patients. This finding is not only suggestive of the contribution of pDCs in the progression of oral cancer but also presents an opportunity and a new target for OSCC immune therapy in oral cancer management.