Involvement of CX3CR1 cells appearing in the abdominal cavity in the immunosuppressive environment immediately after gastric cancer surgery.

BACKGROUND

Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1 cells in intraperitoneal lavage fluid during gastric cancer surgery.

METHODS

Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1 cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array.

RESULTS

CX3CR1 patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1 patients. CX3CR1 patients tended to exhibit higher pathological T and N stage than CX3CR1 patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death-1 expression.

CONCLUSIONS

Our results suggest that CX3CR1 cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1 cells could be useful for characterizing the immune environment after gastric cancer surgery.