A "sweeter" approach to cancer immunotherapy: Glycopolymers as diverse tools for immune modulation

Glycopolymers are synthetic polymers bearing pendant carbohydrate moieties (i.e., sugars) that offer a versatile platform for modulating immune responses beyond the capabilities of conventional methods. These biomaterials mimic and modify glycan-mediated interactions, which are key features of tumor immune evasion and signaling. Interactions between glycopolymers and carbohydrate-binding proteins such as lectins, siglecs, and selectins enable fine-tuning of immune cell activation, trafficking, and tumor recognition. Recent advances in polymer chemistry have enabled the synthesis of glycopolymers with highly defined architectures, multivalent presentation, and spatial organization, thereby enhancing biological specificity and potency. This review highlights the application of glycopolymers in cancer immunotherapy, including their roles as vaccine adjuvants to amplify anti-tumor immune responses, drug carriers for targeted delivery of anticancer agents, and scaffolds for immune cell reprogramming. Special attention is given to the emerging class of dynamic and stimulus-responsive glycopolymers that adapt their function in response to cues within the tumor microenvironment, offering temporally and spatially controlled therapeutic effects. Despite these advances, translational challenges remain, including enhancing biocompatibility, improving scalable synthesis, increasing in vivo stability, and addressing regulatory hurdles. We argue that future progress in this field will depend on sustained interdisciplinary efforts to integrate glycomics, materials science, and immunoengineering. Overall, these insights consolidate recent developments in glycopolymer-based immunomodulation and articulate a forward-looking roadmap to accelerate their clinical translation as precision tools for cancer immunotherapy.