CHST4 (carbohydrate sulfotransferase 4) is a Golgi-localized sulfotransferase that catalyzes 6-O-sulfation of N-acetylglucosamine residues on O-linked mucin-type glycans, primarily on peripheral node addressins (PNAds) expressed on high endothelial venules. This enzymatic activity generates the sialyl 6-sulfo Lewis X determinant (MECA-79 epitope), which serves as the critical ligand for L-selectin (SELL)-mediated lymphocyte homing to peripheral lymph nodes 1. CHST4 modulates lymphocyte tethering, rolling velocity, and differential T and B cell recruitment, with particular importance for B lymphocyte homing to secondary lymphoid organs. In cancer biology, CHST4 expression shows paradoxical prognostic significance. In mesothelioma and malignant pleural mesothelioma, higher CHST4 expression correlates with improved overall and recurrence-free survival, potentially through enhanced anti-tumor immune infiltration 23. Similarly, in hormone receptor-positive breast cancer, CHST4 downregulation associates with lymph node metastasis and reduced CD8+ and CD4+ T cell infiltration 1. Conversely, CHST4 is upregulated in cholangiocarcinoma and hepatocellular carcinoma, suggesting tumor-promoting roles in these malignancies 45. These divergent findings suggest CHST4's function in tumor immunity varies by cancer type, making it a context-dependent prognostic marker and potential therapeutic target.