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Peritoneal metastasis is the most common form of metastasis in ovarian cancer (OC), resulting in a poor prognosis. Abnormal modification of proteins by glycosyltransferases is closely related to immunosuppression and tumor metastasis. However, there were few reports on glycosyltransferase related biomarkers of peritoneal metastasis in OC. This study investigates the role of glycosyltransferase GLT8D2 in promoting peritoneal metastasis and tumor immune evasion through PD-L1 N-glycosylation in OC. Using single-cell RNA sequencing and clinical samples, we found that GLT8D2 is significantly upregulated in metastatic OC tissues and negatively correlated with immune pathways. Mechanistically, GLT8D2 interacts with PD-L1, mediates its N-glycosylation at the Asn192 site, thereby enhancing PD-L1 stability. The N-glycosylation of PD-L1 facilitated tumor cell migration and invasion, accompanied by decreased CD8 + T cell infiltration and upregulated expression of T cell exhaustion markers including LAG3 and PD-1. Furthermore, GLT8D2 knockdown synergized with anti-PD-L1 therapy to reduce tumor metastasis in vivo. Hypoxia-inducible factor HIF-1α was identified as a direct transcriptional activator of GLT8D2. Our findings highlight GLT8D2 as a key regulator of metastasis and immune evasion in OC, offering a potential strategy to improve prognosis.
Xu et al. (Fri,) studied this question.