Sialylation in Colorectal Cancer Rewires Antitumor Immunity at the Peritoneal Metastatic Site

Colorectal cancer (CRC) patients are frequently diagnosed with metastases to the peritoneal cavity. These patients have a dismal prognosis and only limited therapeutical benefits. Solid tumors, including CRC, often display elevated levels of sialylated glycan structures, acting as immune checkpoints for immune evasion. However, the detrimental effects of tumor sialylation on antitumor immunity at the peritoneal site remain unexplored. We uncovered that sialylation is higher in peritoneal metastases (PM) compared with primary CRC or liver metastases. Intraperitoneal injection of sialic acid-deficient CT26 CRC cells led to significantly less peritoneal tumor development and a lower peritoneal cancer index (PCI) score. Sialic acid-devoid tumors harbored higher numbers of live CD45⁺ cells, and the myeloid compartment of desialylated tumors showed increased levels of MHC-II⁺ macrophages and dendritic cells and significantly fewer neutrophils and CD206⁺ macrophages, correlating with a lower PCI score. In conclusion, the absence of sialylated glycans reprograms antitumor immunity and reduces tumor formation at the peritoneal site.