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The Role of Glycans in Immune Regulation
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The Role of Glycans in Immune Regulation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 July 2025) | Viewed by 3658

Special Issue Editor

Dr. Senlian Hong

E-Mail Website
Guest Editor
State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Interests: glycotherapy and medicine; chemical glycobiology; chemoproteomics; cancer biology; genoproteomics

Special Issue Information

Dear Colleagues,

Immune cells are covered by a heavy layer of glycans, serving as essential determinants of the fate of immune responses and potential targets for modulating immune tolerance and activation in various pathologic settings. This coregulatory network involves different glycan structures and their multivalent cis- or trans-interactions with binding receptors. Some glycan and binding receptor interactions (e.g., sialic acids and the Siglecs axis) have been newly recognized as immune checkpoints orthogonal to the well-established protein immune checkpoints (e.g., PD-1/PD-L1). However, deciphering these coregulatory networks is important and is largely complicated by the lack of tools.

This Special Issue aims to provide a platform for functional research on glycans in immune systems. We believe that this Special Issue will contribute to an in-depth understanding of glycoimmunology and the development of interventions to cure related diseases in the future, including cancers, autoimmune inflammation, and chronic infection. We welcome your submissions of original papers and reviews focusing on the immunomodulatory functions of glycans.

Dr. Senlian Hong
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

  • glycoimmunology
  • glycotherapy
  • vaccines
  • glycan synthesis
  • immune tolerance

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Published Papers (2 papers)

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Research

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16 pages, 20299 KiB  
Article
Biodistribution of a Mucin 4-Selective Monoclonal Antibody: Defining a Potential Therapeutic Agent Against Pancreatic Cancer
by Achyut Dahal, Jerome Schlomer, Laura Bassel, Serguei Kozlov and Joseph J. Barchi, Jr.
Int. J. Mol. Sci. 2025, 26(13), 6042; https://doi.org/10.3390/ijms26136042 - 24 Jun 2025
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Abstract
We have previously reported on a novel monoclonal antibody (mAb) we designated F5, which was raised against a glycopeptide derived from the tandem repeat (TR) region of Mucin-4 (MUC4), a heavily O-glycosylated protein that is overexpressed in many pancreatic cancer cells. This mAb [...] Read more.
We have previously reported on a novel monoclonal antibody (mAb) we designated F5, which was raised against a glycopeptide derived from the tandem repeat (TR) region of Mucin-4 (MUC4), a heavily O-glycosylated protein that is overexpressed in many pancreatic cancer cells. This mAb was highly specific for the MUC4 glycopeptide antigen in glycan microarrays, ELISA and SPR assays, selectively stained tissue derived from advanced-stage tumors, and bound MUC4+ tumor cells in flow cytometry assays. The mAb was also unique in that it did not cross-react with other commercial anti-MUC4 mAbs that were raised in a similar but non-glycosylated TR sequence. Here we describe the selective conjugation of a novel near-infrared dye to this mAb and in vivo biodistribution of this labeled mAb to various MUC4-expressing tumors in mice. The labeled mAb were selectively distributed to both cell-derived xenograft (CDX) flank tumors and patient-derived xenograft (PDX) tumors that expressed MUC4 compared to those that were MUC4-negative. Organ distribution analysis showed high uptake in MUC4+ relative to MUC4− tumors. These results suggest that mAb F5 may be used to develop MUC4-targeted, passive antibody-based immunotherapies against Pancreatic Ductal Adenocarcinomas (PDACs) which are notorious for being refractory to many chemo- and radiotherapies Full article
(This article belongs to the Special Issue The Role of Glycans in Immune Regulation)
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Review

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16 pages, 1517 KiB  
Review
Glycoscience in Advancing PD-1/PD-L1-Axis-Targeted Tumor Immunotherapy
by Qiyue Sun and Senlian Hong
Int. J. Mol. Sci. 2025, 26(3), 1238; https://doi.org/10.3390/ijms26031238 - 31 Jan 2025
Viewed by 2838
Abstract
Immune checkpoint blockade therapy, represented by anti-PD-1/PD-L1 monoclonal antibodies, has significantly changed the immunotherapy landscape. However, the treatment is still limited by unsatisfactory response rates, immune-related adverse effects, and drug resistance. Current studies have established that glycosylation, a common post-translational modification, is crucial [...] Read more.
Immune checkpoint blockade therapy, represented by anti-PD-1/PD-L1 monoclonal antibodies, has significantly changed the immunotherapy landscape. However, the treatment is still limited by unsatisfactory response rates, immune-related adverse effects, and drug resistance. Current studies have established that glycosylation, a common post-translational modification, is crucial in promoting cancer progression and immune invasion. Targeting aberrant glycosylation in cancers presents precision medicine regimens for monitoring cancer progression and developing personalized medicine. Notably, the immune checkpoints PD-1 and PD-L1 are highly glycosylated, which affects PD-1/PD-L1 interaction and the binding of anti-PD-1/PD-L1 monoclonal antibodies. Recent achievements in glycoscience to enhance patient outcomes, referred to as glycotherapy, have underscored their high potency in advancing PD-1/PD-L1 blockade therapies, i.e., glycoengineered antibodies with improved binding toward PD-1/PD-L1, pharmaceutic inhibitors for core fucosylation and sialylation, and synergistic treatment with the antibody–sialidase conjugate. This review briefly introduces the PD-1/PD-L1 axis and glycosylation and highlights the fundamental and applied advances in glycoscience that improve PD-1/PD-L1 immunoblockade therapies. Full article
(This article belongs to the Special Issue The Role of Glycans in Immune Regulation)
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