Glycosylation-driven immune evasion and strategies for targeted cancer immunotherapy

Glycosylation research is steadily emerging as a critical area in the field of tumor immunology, offering fresh insights into how cancers subvert immune detection and destruction. One defining feature of malignant transformation is the profound remodeling of the glycocalyx—the dense, glycan-rich layer covering the tumor cell surface—through aberrant glycosylation events. These modifications can shield tumors from immune surveillance by masking antigenic epitopes, modulating inhibitory checkpoint engagement, and altering essential physical properties at the cell surface. Recent studies, leveraging advanced functional genomics, glycoproteomics, and multi-omics profiling, have highlighted the pivotal role of glycosylation in shaping anti-tumor immune responses and determining immunotherapy efficacy. Despite mounting evidence that tumors co-opt glycosylation to evade immune attack, current immunotherapies only partially address this axis, and there remains a critical gap in integrating glycan biology into next-generation treatment strategies.This Research Topic aims to deepen our understanding of the multifaceted roles glycosylation plays in immune escape and to accelerate the translation of glyco-targeted approaches for enhanced cancer immunotherapy. We seek to gather cutting-edge research that dissects glycosylation-dependent interactions among tumor and immune cells—spanning T lymphocytes, natural killer cells, myeloid populations, and stromal compartments—and to interrogate how specific glycan structures and remodeling enzymes regulate checkpoint pathways, antigen presentation, and effector cell dysfunction. Special emphasis is placed on studies harnessing recent methodological advances, including high-throughput genomic perturbations, spatially resolved single-cell analyses, and precision glycomics, to pinpoint actionable glyco-markers, predictive pathways, and combinatorial strategies. Ultimately, this Topic aspires to foster innovations in biomarker discovery and to promote the rational integration of glycan modulation with established and emerging immunotherapies.We define the scope of this Research Topic as encompassing the mechanistic, methodological, and translational exploration of glycosylation in tumor immune escape and its therapeutic targeting. Relevant themes include, but are not limited to:• Molecular and cellular mechanisms regulating tumor and microenvironmental glycosylation• Glycosylation-driven immune evasion, including glycocalyx remodeling and glycan-mediated shielding• Regulation of immune checkpoints and lectin pathways through tumor glycosylation• State-of-the-art glycomics, computational, and AI-based strategies for identifying predictive glyco-signatures• Therapeutic development: small molecules, antibodies, enzymes, and glycoengineering approaches in combination with immunotherapy Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Jinghang Li, Shruti Bhatt, Po Hu Source: https://www.frontiersin.org/research-topics/78079/glycosylation-driven-immune-evasion-and-strategies-for-targeted-cancer-immunotherapy