The study of glycosylation across diverse diseases has revealed that both malignant and infected cells harness complex glycan patterns to manipulate immune recognition and response. In cancer, tumors remodel their surface glycome to evade immune attacks, in part by engaging glyco-immune checkpoints such as Siglecs on myeloid and natural killer cells, thereby suppressing anti-tumor activity. Similarly, persistent viral infections—including HIV—exploit glycan-mediated mechanisms for immune evasion, most notably through the densely glycosylated HIV envelope that forms a protective “glycan shield.” This structure not only impedes neutralizing antibody responses but also interacts with host lectins to alter innate and adaptive immunity. Such parallels between cancer cells and HIV-infected cells underscore the broader immunological significance of glycan-lectin networks, and highlight the importance of targeting aberrant glycosylation to enhance immune clearance and therapeutic efficacy.

Glycan biology and the immune system are intricately linked, influencing disease treatment and management. Glycosylation shapes immune recognition and modulation, directly affecting outcomes in cancer, autoimmune diseases, and chronic viral infections like HIV. The dense glycan shield on the HIV envelope exemplifies a significant barrier to immune detection and vaccine efficacy, mirroring how tumors and other pathogens use glycan modifications to evade immunity. Understanding these shared and unique mechanisms is vital for developing next-generation immunotherapies, diagnostics, and vaccines.

Both malignant and infected cells exploit altered glycan patterns to escape immune responses. Tumors reconfigure their cell-surface glycome to suppress immunity, often through activation of immune checkpoints like Siglecs. Viruses such as HIV use complex glycosylation, particularly the viral glycan shield, to block neutralizing antibodies and interact with host lectins, modulating both innate and adaptive immune pathways. These parallels reveal a fundamental challenge: aberrant glycosylation enables persistent immune evasion in cancer and chronic infections. Tackling these glycan-mediated barriers is therefore essential for advancing innovative therapies and improving outcomes across a broad spectrum of immune-mediated diseases.

This Research Topic brings together advances at the intersection of glycan biology, immune regulation, and disease. It seeks contributions that uncover how glycosylation shapes immune responses, influences the success of therapeutic interventions, and impacts disease progression. The scope includes discoveries in tumor glycosylation, immune cell glycome remodeling, regulation of immunity through lectin–glycan interactions, and the development of glycan-targeted treatments and vaccines. Clinical, translational, and basic research from diverse fields—including chronic infection, inflammatory diseases, and oncology—are welcome.

Particular interest lies in comparative approaches that reveal unique or shared glycan-driven mechanisms across multiple conditions, as well as studies highlighting glycomic biomarkers for diagnosis, prognosis, or treatment response. Specific Themes for Contributors:

1. Glycan biosynthesis and regulatory mechanisms
2. Glycan-based immune escape and persistence in HIV
3. Glycan-immune cell interactions and signaling
4. Broadly neutralizing antibodies targeting HIV glycans
5. Discovery and validation of glycan biomarkers
6. Glycoengineering approaches for HIV therapy
7. Development of glycan-targeted immunotherapies and drug delivery systems
8. Comparative glycoimmunology in HIV and autoimmune/cancer contexts
9. Understanding glycan-driven therapy resistance
10. Novel glycomic biomarkers in HIV immune dysregulation
11. Advances in glycomics and multi-omics technologies
12. Clinical translation and biomarker-driven trials
13. Comparative roles of glycans in autoimmunity versus cancer microenvironments.

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.

Are you interested in contributing a manuscript to this Research Topic?

The Role of Glycans in Immunotherapy and Immune Modulation: Implications for Autoimmune Diseases, Cancer, and HIV.