HMGB1 and colonic neoplasm: HMGB1 secretion after tissue damage modulates signaling pathways that attenuate T-lymphocyte responses and enhance MDSC expansion.44 In colon cancer, elevated HMGB1 levels released into the peritoneal cavity recruit vast amounts of MDSCs, promoting peritoneal metastasis after curative surgery.45 HSP70, another important DAMP, effectively suppresses G-MDSC and M-MDSC populations.46 In addition, DAMPs extracellular ATP enhances MDSC dysfunction through the ATP receptor (P2 × 7R) and NLRP3 inflammasome activation.47 Complement factors also are secreted during surgical trauma.