Peri-operative monocyte count is a marker of poor prognosis in gastric cancer: increased monocytes are a characteristic of myeloid-derived suppressor cells.

Abstract

Gastric cancer (GC) is the most common malignant tumor in digestive organs, and the prognosis of GC patients who have undergone surgery remains poor because of frequent recurrence. Therefore, the identification of new markers to predict the outcome of these patients is needed. Monocyte count is a negative prognostic factor associated with inflammation. We investigated the relationship between peripheral monocytes in the peri-operative period and prognosis in GC patients. A high pre-operative monocyte count was identified as a prognostic factor in a retrospective analysis of 278 stage II and III GC patients who underwent curative gastrectomy. In contrast, an increased post-operative monocyte count compared to the pre-operative monocyte count was a marker of poor prognosis, particularly for early relapse. In a prospective analysis of 75 GC patients, a subset of the increased post-operative monocytes was similar to CD14⁺ HLA-DR^- CD11b⁺ CD33⁺ cells by flow cytometry, and these monocytes produced IDO and arginase and suppressed T cell functions; therefore, we classified these cells as monocytic myeloid-derived suppressive cells (M-MDSCs). Peri-operative neutrophils and C-reactive protein (CRP), which are also related to inflammation, did not affect the prognosis of GC patients, and a neutrophil immunosuppressive function was not observed. These results suggest that peripheral monocytes in the peri-operative period in GC patients are a useful marker for the prognosis of GC patients, and a subset of increased post-operative monocytes may be characterized as M-MDSCs.