The role and therapeutic potential of protein glycosylation in the immune regulation of breast cancer.

Breast cancer has emerged as the most prevalent malignant tumor among women worldwide. Its intricate and highly heterogeneous pathogenesis presents substantial challenges for effective treatment. In recent years, the increasing prominence of tumor immunotherapy has highlighted the pivotal role of protein glycosylation, particularly its regulation of glycan structural alterations in the initiation, progression, and immune evasion mechanisms of breast cancer. Evidence suggests that glycan modifications-such as N-glycosylation, O-glycosylation, fucosylation, and sialylation-not only significantly influence tumor cell biology but also directly modulate the function and stability of key immune checkpoint molecules, including PD-1/PD-L1, CD24, and members of the B7 family. Aberrant glycosylation in breast cancer cells fosters the establishment of an immunosuppressive microenvironment, a critical factor that limits the efficacy of immunotherapy. Consequently, interventions targeting glycosylation modifications present promising strategies to enhance the therapeutic response to immunotherapy in breast cancer patients. Thus, our comprehensive exploration of the underlying mechanisms of glycosylation modifications in breast cancer immunotherapy provides a robust theoretical foundation and identifies novel intervention targets to overcome the therapeutic challenges faced in breast cancer and other immunologically "cold" tumors.