Table 3.

Examples of glycan-engineering and its implications in immune therapy

	Intervention	Effect
GENETIC ENGINEERING	Deletion of N-glycosylation sites in TCR chains	Increased functional avidity by improved TCR multimerization and decreased TCR-MHC dissociation108
	Overexpression of ST6GalI (increased α-(2,6) sialylation)	Shielding LacNac residues from Galectin-1 binding, reducing Galectin-1 induced cell death of T cells45
	Genetic ablation of FUT8	Reduced cell surface expression of PD-1 and enhanced T cell activation109
METABOLIC GLYCOENGINEERING	Inhibition of LacNAc synthesis Addition of Galectin-binding variant of lactose	Increased number of infiltrating tumor-specific CD8+ T cells and intra-tumoral IFN-γ expression110 Increased TIL numbers and reduced tumor growth111
	Inhibition of fucosylation and sialylation Sialic acid biosynthesis blockade	Decreased Selectin ligand synthesis and impaired cancer cell adhesion and migration in vitro and prevention of metastasis in vivo112 Enhanced T cell killing capacity113
	Enhanced N-glycan branching	Control of the T cell immune response114
CHEMOENZYMATIC GLYCOENGINEERING	LacNAc labeling LacNAc modification with antibodies to generate antibody-T cell conjugate	Biophysical probe for imaging or glycomics analysis115 Increased tumor targeting capacity and resistance to inhibitory signals116
	Fucosyltransferase treatment of regulatory T cells	Increased expression of sLex antigens leading to improved trafficking, homing and engraftment117
	PNGaseF treatment of regulatory T cells	Increased proliferation of naïve and memory T cells118
	Sialidase treatment of cytotoxic T cells	Increased T cell activation and cytolytic activity119