Terminal sialic acids on tumor cell surface glycoconjugates (Sia)

Terminal sialic acids are nine-carbon monosaccharides that terminate glycan chains on cell surface glycoproteins and glycolipids, forming a critical component of the glycocalyx (Zhou et al., 2020). In many cancers, an upregulation of sialyltransferases leads to hypersialylation, a hallmark of malignant transformation that facilitates immune evasion and metastasis (Duenas et al., 2020). These terminal sugars act as ligands for Sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed on various immune cells, including natural killer (NK) cells, neutrophils, and T cells (Nature Reviews Drug Discovery, 2019). The interaction between tumor sialoglycans and Siglecs triggers inhibitory signaling pathways, effectively creating a glyco-immune checkpoint that protects the tumor from immune surveillance (Palleon Pharmaceuticals, 2023). Therapeutic approaches targeting this axis include sialidase-based biologics, such as E-602, designed to enzymatically remove sialic acids from the tumor surface, as well as small molecule inhibitors of sialylation (Gray et al., 2020). By stripping the sialic acid cloak, these therapies aim to re-sensitize the tumor to the host's innate and adaptive immune responses.

Other names

Tumor-associated sialoglycansHypersialylationSialic acid-containing glycansSialoglycan-Siglec axisN-acetylneuraminic acid (Neu5Ac) conjugates

Enzymatic desialylation of the tumor cell surface to disrupt the Siglec-mediated immune checkpoint and enhance anti-tumor immunity (Palleon Pharmaceuticals, 2023; Gray et al., 2020).