The glycocalyx and immune evasion in cancer

In order to establish malignant lesions, tumors must first evade their detection by immune cells. Tumors achieve this by embellishing and tailoring their glycocalyx, a network of polysaccharides and glycosylated proteins that refracts the phagocytic efforts of myeloid cells, shrouds neoantigens and other ligands from cells of the acquired immune system, and skews immune responses. The barriers imposed by the glycocalyx are biophysical and also linked to the inhibitory receptor signaling pathways of immune cells that engage tumor sialic acids as markers of healthy self. This would explain the pressure for cancers to upregulate the synthases, transmembrane mucins, and other heavily sialylated glycoproteins involved in establishing a repulsive glycocalyx. Accordingly, individual tumor cells that are best capable of constructing a shielding glycocalyx on their surface show higher metastatic potential in immunocompetent mice. Reciprocally, therapeutics have recently been devised to edit and dismantle the glycocalyx barrier in an effort to invigorate an immune response aimed at tumor destruction. We discuss the features of the tumor-associated glycocalyx that afford immune evasion of cancers and how strategies that target this barrier may potentiate antitumor immunity.

Automated summary

In order for tumors to establish malignant lesions, they must first evade detection by immune cells. They do this by modifying their glycocalyx, a network of polysaccharides and glycosylated proteins that prevents immune cells from engulfing them and hides antigens from the immune system. The barriers imposed by the glycocalyx are both physical and linked to immune cell signaling pathways. Therapies have been developed to edit and dismantle the glycocalyx barrier in order to enhance the immune response against tumors.