Editorial: Glycobiology and glycosylation: deciphering the secrets of glycans in humans and pathogens

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Glycosylation, the process of adding carbohydrates to proteins, is a fundamental biological with far-reaching implications for human health and disease. These glycan modifications play critical roles in numerous cellular processes, including protein folding, cell signaling, immune recognition. Their dysregulation implicated various diseases, cancer, infectious autoimmune disorders (1,2).One striking example glycosylation's importance cancer immunotherapy field.The effectiveness treatments, especially immunotherapies like anti-PD-L1 monoclonal antibodies (e.g., atezolizumab), can be significantly impacted by altered glycosylation patterns on tumor cells (3,4). alterations shield from surveillance dampen response immunotherapy. For instance, atezolizumab's withdrawal breast treatment due limited efficacy highlights challenges posed (5).Within this landscape, galectin family particularly galectin-9, emerges as player progression resistance therapy, underscoring intricate link between evasion, where galectin-9 acting potential barrier effective immunotherapy, treatments atezolizumab (6,7).Recognizing increasing significance glycobiology disease, Frontiers Immunology has published special issue titled "Glycobiology Glycosylation: Unraveling Mysteries Glycans Humans Pathogens." This collection insightful articles delves into world glycans, each article offering unique perspective connection therapeutic strategies:Homan et al. analyze how vitro passaging chondrocytes alters their profiles subsequently influences interaction system. results indicate that passaged provoke more intense pro-inflammatory macrophages, marked increased IL-6 nitric oxide production, compared non-passaged chondrocytes.This research dynamic nature expression its cell-based therapies, such cartilage transplants.Potaczek investigate IgA plasma critically ill COVID-19 patients. They found notable differences glycosylation, characterized reduced sialylation heightened galactosylation patients experiencing acute respiratory distress syndrome (ARDS). changes were linked formation neutrophil extracellular traps (NETs), suggesting possible thromboembolic complications severe cases.Grigorieva explore complex regulation heparan sulfate biosynthesis fibroblasts cocultured normal or cancerous prostate cells. findings suggest do not influence regulatory mechanism, while epithelial downregulate genes associated synthesis fibroblasts. disparity communication may contribute unchecked growth indicating targeting glycosaminoglycan pathways.Souchak provide an in-depth review galectins, specifically Gal-3, -8, -9, facilitating circulating adhesion vascular endothelium. examine mechanisms which galectins promote through direct interactions indirect signaling enhances molecules endothelial crucial physiological pathological events, trafficking, stem homing, metastasis (CTCs). The also considers strategies address inflammation spread disrupting galectinmediated adhesion.targeted drug delivery systems treatment. emphasize properties glycans-such specificity, versatility, low immunogenicity-that make them ideal purpose. Glycan-based have enhance minimizing off-target effects explicitly tissues. authors designing producing these scaffolds, calling further development promising field.Campanero-Rhodes innate system detects hypermucoviscous variants Klebsiella pneumoniae. focuses bacterial surface glycans lectins, Siglec families. highlight role structures pathogen recognition relationship host immunity virulence. Understanding vital developing novel combat infections caused hypervirulent strains.regulating collagen deposition resolution fibrosis idiopathic pulmonary (IPF).Their reveal elevated levels OGT IPF patients, implicating excessive accumulation characteristic lung Through single-cell RNA sequencing experimental models, they demonstrate inhibiting effectively reverse accumulation. discovery positions target other fibrotic diseases matrix deposition.René Roy explores shared abnormal enveloped viruses. atypical profiles, often resulting deficiencies glycosyltransferase activities, mutations, overexpression chaperones, glycoepitopes tumor-associated carbohydrate antigens emerged targets glycoconjugate vaccines. Notably, N-linked viral glycoproteins resemble those cells, specific O-linked closely mirror present intriguing overlap suggests vaccines could stimulate robust responses against infections.The diverse featured our understanding disease mechanisms. studies illuminate subtle profoundly affect responses, progression, hosts pathogens. We are confident all contributions within will serve resource researchers field inspire exploration captivating glycans.

Language: Английский

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Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 25, 2025

Abstract This review discusses reprogramming the breast tumor immune microenvironment from an immunosuppressive cold state to immunologically active hot state. A complex interplay is revealed, in which accumulation of metabolic byproducts—such as lactate, reactive oxygen species (ROS), and ammonia—is shown impair T-cell function promote escape. It demonstrated that (TME) dominated by cytokines, including interleukin-10 (IL-10), transforming growth factorβ (TGFβ), IL-35. Notably, IL-35 produced regulatory T cells cancer cells. The conversion conventional into IL-35-producing induced cells, along with inhibition pro-inflammatory cytokine secretion, contributes suppression anti-tumor immunity. further key checkpoint molecules—such PD-1, PDL1, CTLA-4, TIM-3, LAG-3, TIGIT—are upregulated within TME, leading Tcell exhaustion diminished responses. blockade these checkpoints restore functionality proposed a strategy convert tumors ones robust effector cell infiltration. therapeutic potential chimeric antigen receptor (CAR)T therapy also explored, targeting specific tumor-associated antigens, such glycoproteins tyrosine kinases, highlighted. suggested CART efficacy can be enhanced combining inhibitors other immunomodulatory agents, thereby overcoming barriers imposed TME. Moreover, role microbiome regulating estrogen metabolism systemic inflammation reviewed. Alterations gut microbiota are affect microbiome-based interventions additional means facilitate cold-to-hot transition. concluded immunological pathways underpin suppression—through combination strategies involving blockade, therapies, modulation—the TME achieved. anticipated enhance infiltration function, improving overall immunotherapies better clinical outcomes for patients.

Language: Английский

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ALG3 predicts poor prognosis and increases resistance to anti-PD-1 therapy through modulating PD-L1 N-link glycosylation in TNBC

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112875 - 112875

Published: Aug. 9, 2024

Language: Английский

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Potential therapies for non-coding RNAs in breast cancer

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 20, 2024

Breast cancer (BC) is one of the frequent tumors that seriously endanger physical and mental well-being in women with strong heterogeneity, its pathogenesis involves multiple risk factors. Depending on type BC, hormonal therapy, targeted immunotherapy are current systemic treatment options along conventional chemotherapy. Despite significant progress understanding BC therapeutic options, there still a need to identify new targets develop more effective treatments. According recent sequencing profiling studies, non-coding (nc) RNAs genes deregulated human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, similarly, expression many ncRNAs altered breast cell lines tissues. The ability single regulate downstream gene related pathways provides theoretical basis for studying them drug development delivery. Therefore, it far-reaching explore role tumor their potential as targets. Here, our review outlines two major ncRNAs, long (lncRNAs) microRNAs (miRNAs) diagnostic prognostic biomarkers well strategies cancer.

Language: Английский

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Protein biomarkers for subtyping breast cancer and implications for future research: a 2024 update

Expert Review of Proteomics, Journal Year: 2024, Volume and Issue: 21(9-10), P. 401 - 416

Published: Oct. 2, 2024

Breast cancer subtyping is used clinically for diagnosis, prognosis, and treatment decisions. Subtypes are categorized by cell of origin, histomorphology, gene expression signatures, hormone receptor status, and/or protein levels. Categorizing breast based on signatures aids in assessing a patient's recurrence risk. Protein biomarkers, the other hand, provide functional data selecting therapies primary recurrent tumors. We an update biomarkers subtypes their application prognosis therapy selection.

Language: Английский

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