Tumor sialylation controls effective anti-cancer immunity in breast cancer

To better understand the mechanisms underlying immune evasion in breast cancer, we analyzed two independent clinical cohorts and identified a negative association between tumor sialylation and T cell infiltration across molecular subtypes, most prominently in luminal B tumors.

In preclinical models, both genetic and pharmacologic inhibition of tumor cell sialylation reshape the tumor microenvironment by reducing neutrophil and PMN-MDSC infiltration, while CD8⁺ effector and Tcf7⁺ memory T cells are increased within the mammary tumors. Mechanistically, sialylation enhances the serum half-life of granulocyte colony-stimulating factor (G-CSF), a key driver of neutrophilic immunosuppression, and dampens tumor cell immunogenicity by limiting MHC-I surface expression.