CCR9-CCL25 mediated plasmacytoid dendritic cell homing and contributed the immunosuppressive microenvironment in gastric cancer.

ABSTRACT

OBJECTIVES: Plasmacytoid dendritic cells (pDCs) play a crucial role in the microenvironment of tumor. Evidences has been shown that chemokine receptor 9 (CCR9) is an important molecule that attracts pDCs homing to the digestive tract and the latter are involved in the formation of digestive tract immune tolerance. The aim of this study was to explore the role of CCR9-CCL25 interaction in pDC-mediated immunosuppression microenvironment of gastric cancer (GC). MATERIALS AND METHODS: Regulatory T cells (Tregs) and pDCs were detected by immunohistochemistry. CCR9, which expressed on pDC was visualized by immunofluorescence. Western Blot was applied to evaluate the expression of CCL-25. Total pDCs, CCR9+pDCs, CCR9-pDCs, total Tregs, inducible costimulator + (ICOS) Tregs and ICOS-Tregs in peripheral blood and draining lymph nodes were analyzed by flow cytometry. Plasma concentration of the cytokines were measured by enzyme-linked immunosorbent assay RESULTS: Total Tregs, pDCs and CCR9+pDCs were higher in GC tissue. CCL-25 was over-expressed in carcinoma tissue. Peripheral total pDCs, CCR9-pDCs, total Tregs, ICOS+ Tregs, ICOS- Tregs were significantly increased in GC patients. More total pDCs, CCR9+ pDCs, total Tregs, ICOS+ Tregs were found in metastatic lymph nodes. Plasma concentrations of IL-6 and IL-10 were significantly higher in GC patients. More CCR9+ pDCs were found infiltrating carcinoma tissue in patients with later T staging and lymph node metastasis and conferred a poor prognosis. CONCLUSION: CCR9-CCL25 interaction might play an important role in mediating PDC homing to metastatic lymph nodes and carcinoma tissue, which contributed to the formation of tumor immunosuppressive microenvironment and poor prognosis.