FIGURE 5 from Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer

NOX2 inhibition prevents surgery-induced metastasis in a murine model. A, Schematic outline of the experimental model of surgery-induced metastasis. Blood samples were collected from naïve (Ctrl) and sponge-bearing (Inf) WT and NOX2-KO mice 1 week after a surgical procedure (sponge implantation). A group of WT mice received intraperitoneal injections with histamine dihydrochloride (WT HDC) every other day starting one day before surgery and continuing until 3 days after tumor cell challenge. Frequency of CD11b⁺Ly6C⁺M-MDSC (B) and intracellular ROS levels in M-MDSC (C) were measured by flow cytometry. At 8 days postsurgery, mice were intravenously inoculated with B16F10 cells. D, Metastatic lesions in lungs were enumerated 19–21 days after tumor cell challenge. Differences in inflammatory monocytes, DCFDA levels, and tumor numbers in vivo were calculated using one-way ANOVA following Holm-Šídák multiple comparisons test. The frequency of M-MDSC and number of metastatic foci was evaluated in four independent experiments for WT mice with or without surgery-induced inflammation, and in two experiments for KO mice and HDC treated mice. DCFDA levels of M-MDSC were measured in three independent experiments for WT mice, two experiments for KO mice, and one experiment for HDC-treated mice. In each experiment, 4–5 mice per group were included. Fold change was calculated by dividing raw data with the mean of raw data in the WT mice control group in each experiment. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.