Sialic acids modulate immune responses in cancer: Therapeutic opportunities

The development of therapies that boost anti-tumor immunity has transformed cancer treatment. While the efficacy of traditional therapies, such as chemotherapy and radiation therapy, is limited by toxicity and resistance, forms of immunotherapy, including immune checkpoint blockade therapies and engineered cellular therapies, have shown unprecedented success for certain patient populations. Despite these advances, therapeutic resistance remains a significant barrier, and alternative therapies are needed to overcome immune evasion mechanisms. One prominent evasive mechanism utilized by tumor cells is hypersialylation, the overexpression of glycans capped with sialic acid on the cell surface. This review focuses on the immunosuppressive role of sialic acid in cancer and highlights opportunities to target sialic acid and its binding proteins, offering a promising therapeutic perspective to counteract resistance and improve patient outcomes.