Potential role of plasmacytoid dendritic cells for FOXP3+ regulatory T cell development in human colorectal cancer and tumor draining lymph node.

FOXP3(+) regulatory T cells (Tregs) play an important role in the maintenance of tumor immunity tolerance. Compared with conventional myeloid dentritic cells (mDCs), plasmacytoid dendritic cells (pDCs) exhibit poor immunostimulatory ability, and their interaction with T cells often promotes the development of Tregs. The aim of this study was to determine FOXP3(+) Tregs and CD123(+)pDCs infiltration in colorectal cancer and tumor draining lymph node (TDLN), and to evaluate the clinical significance and relationship between pDCs infiltration and Tregs development in the CRC tolerogenic milieu. An immunohistochemical assay was conducted to assess FOXP3(+)Tregs and CD123(+)pDCs infiltration in tumor tissue and in metastatic-free TDLN (mfTDLN) and metastatic TDLN (mTDLN). The results showed that FOXP3(+) Tregs infiltration was more frequent in tumor tissue than in adjacent normal mucosa (P<0.001). FOXP3(+)Tregs infiltration was associated with advanced TNM stage and lymph node metastasis (P<0.01 and P<0.01 for TNM stage and lymph node metastasis, respectively). Different from FOXP3(+)Tregs, CD123(+)pDCs frequencies were lower in most CRC tumor tissues, whereas the positive rate of CD123 expression in CRC was significantly higher than in adjacent normal mucosa tissue (P<0.01). Compared to mfTDLN, mTDLN was significantly enriched in FOXP3(+) Tregs (P<0.01) and increased in pDC/mDC ratio (P<0.01). The statistical analysis demonstrated a significant correlation in both Tregs and pDC/mDC ratio in mTDLN. These results suggest that there are more FOXP3(+) Tregs with a stronger prognostic significance which might promote tumor tolerance, and that CD123(+)pDCs might contribute to Tregs development in the CRC tolerogenic milieu.