FIGURE 3 from Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer

Abstract

<p>High levels of M-MDSC and low levels of NKp30<sup>high</sup> NK cells after pancreatic cancer surgery correlate and predict poor survival. <b>A,</b> Forest plots for postoperative survival were generated by log-rank tests where patients were dichotomized on the basis of Youden index for high or low absolute number of M-MDSCs, CD56<sup>bright</sup> NK cells, CD16<sup>+</sup> NK cells, monocytes, lymphocytes, CD8<sup>+</sup> T cells, regulatory T cells, CD4<sup>+</sup> T cells, DC, neutrophils, or plasma levels of IL6, high expression level of NKp30<sup>+</sup> cells among CD16<sup>+</sup> (NKp30<sup>high</sup> CD16<sup>+</sup>) and CD56<sup>bright</sup> (NKp30<sup>high</sup> CD56<sup>bright</sup>) NK cells one day after surgery or by age or sex. Kaplan–Meier survival comparisons by high (red) or low (blue) absolute numbers of M-MDSC (<b>B</b>) and NKp30<sup>high</sup> cells among CD16<sup>+</sup> NK cells (<b>C</b>) one day after surgery by log-rank test. <b>D,</b> Heat map of correlations (Pearson <i>r</i>, above the diagonal) between immune cell populations and IL6 among patients undergoing pancreatic cancer surgery. <i>P</i>-values corresponding to each correlation are shown below the diagonal. Correlation between absolute numbers of M-MDSC and frequencies of NKp30<sup>high</sup> cells among CD16<sup>+</sup> NK cells at all analyzed timepoints (<b>E</b>), or within the first week after surgery (green dots: pre-op, black dots: 1 day, red dots 3–5 days and orange dots 28 days after surgery; <b>F</b>). Statistics by linear regression. Survival impact of high (red) or low (black) intratumoral NCF2 expression in pancreas cancer samples from the IPEP study (<i>n</i> = 14; <b>G</b>) or the Kaplan–Meier plotter database (<i>n</i> = 852; <b>H</b>), using the best cut-off feature of the portal and log-rank statistics. <b>I,</b> Expression analysis of Single Cell portal PDAC samples showed that the majority of NCF2-expressing cells were confined to a specific immune cell cluster.</p>