Tumor-associated sialoglycans

Tumor-associated sialoglycans are a diverse group of cell-surface glycoproteins and glycolipids characterized by an overabundance of terminal sialic acid residues, a phenomenon known as hypersialylation [1.1.1, 1.1.2]. These glycans function as a critical glyco-immune checkpoint by binding to Sialic acid-binding immunoglobulin-type lectins (Siglecs) on the surface of various immune cells, including natural killer (NK) cells, macrophages, and T cells [1.1.2, 1.1.3]. This interaction triggers inhibitory signaling that suppresses the immune system's ability to recognize and destroy cancer cells [1.1.1, 1.1.5]. Therapeutic strategies, such as the use of sialidase fusion proteins like E-602 (efgitasialase alfa), aim to enzymatically remove these sialic acids from the tumor surface [1.1.1, 1.1.4]. By desialylating the tumor, these drugs disrupt the Siglec-sialoglycan axis, thereby reactivating the host's innate and adaptive immune responses against the malignancy [1.1.2, 1.1.5]. This approach represents a novel frontier in immuno-oncology, targeting the glyco-code of cancer cells to overcome immune resistance [1.1.4].

Other names

Sialic acid-containing glycoproteinsSiglec ligandsHypersialylated glycansTumor sialoglycoproteinsSialomeCell-surface sialic acid-containing glycoprotein receptors

Enzymatic desialylation of the tumor cell surface to remove terminal sialic acids, thereby preventing the engagement of inhibitory Siglec receptors on immune cells and restoring anti-tumor immunity [1.1.1, 1.1.2].