[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-349196-105":3,"doc-detail-349196-en":80,"detail-sidebar-cat-0-en-105":98},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","tissue-specific-factors-that-govern-the-sialoglycan-siglec-axis-in-cancer","Tissue-specific factors that govern the sialoglycan-Siglec axis in cancer","","Aberrant sialylation in cancer reshapes tumour microenvironment interactions by altering the sialoglycan display on malignant and stromal cells. Many sialoglycans bind Siglecs, immune-predominant receptors that often deliver inhibitory glyco-immune checkpoint signals, driving immune evasion and metastatic behavior. The review explains how tissue-of-origin programs and lineage states set basal sialyltransferase output, while emerging single-cell data show stromal cells can acquire hypersialylation and generate immunosuppressive Siglec ligands. It also considers transcriptional regulators, therapy-induced ligand availability changes, and treatment resistance.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tissue-specific-factors-that-govern-the-sialoglycan-siglec-axis-in-cancer/349196/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tissue-specific-factors-that-govern-the-sialoglycan-siglec-axis-in-cancer/349196.png","ImageObject",300,407,{"name":42,"@type":43},"Cart","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":30},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What is the sialoglycan–Siglec axis, and why is it relevant to cancer?","Question",{"text":62,"@type":63},"The axis links tumour-associated sialylated glycans (sialoglycans) to Siglecs on immune cells. Siglec engagement often transmits inhibitory signals that suppress anti-tumour immune activity, shaping responses in the tumour microenvironment.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How do tissue-specific factors influence sialylation in cancer?",{"text":67,"@type":63},"Tissue-of-origin programmes and differentiation state establish basal sialyltransferase expression and constrain the sialoglycan repertoire available to tumours. This tissue context contributes to tumour-specific sialoglycan profiles.",{"name":69,"@type":60,"acceptedAnswer":70},"How can stromal cells contribute to immunosuppressive Siglec ligands?",{"text":71,"@type":63},"Emerging single-cell evidence indicates that stromal populations, especially cancer-associated fibroblasts, can acquire hypersialylation. They can actively generate Siglec ligands that promote immune suppression.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},349196,1790146587,{"code":4,"msg":81,"data":82},"success",{"doc_id":78,"user_id":83,"nickname":42,"user_avatar":84,"doc_module":4,"category_id":85,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":86,"file_id":87,"file_url":88,"file_type":89,"file_size":90,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":91,"language":92,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":93,"faqs":94,"seo_title":95,"seo_description":12,"update_tm":96,"read_time":97},18829141979164,"https://eur-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8",8,"Bioscience Reports (2026) 46 BSR20250119 [https://doi.org/10.1042/BSR202501](https://doi.org/10.1042/BSR202501)19  \nReview Article  \nTissue-specific factors that govern the sialoglycan–Siglec axis in cancer  \nJamie Wills, Adam Duxfield, Manuella Siaka Monthe and  Emma Scott  \nBiosciences Institute, Newcastle University, Newcastle NE1 3BZ, U. K.  \nCorrespondence: Emma Scott ([emma.scott@newcastle.ac.uk](emma.scott@newcastle.ac.uk))  \nReceived: 23 October 2025  \nRevised: 16 March 2026  \nAccepted: 07 April 2026  \nVersion of Record published:  \n14 May 2026  \nAberrant sialylation is a persistent glycosylation change in cancer that reshapes interactions within the tumour microenvironment through the display of sialylated glycans (sialoglycans) on malignant and stromal cells. Many sialoglycans engage sialic  \nacid-binding immunoglobulin-like lectins (Siglecs), a family of receptors expressed predominantly by immune cells that frequently transmit inhibitory signals and function as glyco-immune checkpoints. Increasing evidence indicates that tumour hypersialylation suppresses myeloid and lymphoid anti-tumour activity, promotes immune evasion, and contributes to metastatic behaviour. However, both sialoglycan repertoires and Siglec expression patterns vary markedly across cancer types and disease states, suggesting strong dependence on tissue context and tumour composition. In the present review, we discuss how tissue-of-origin programmes and lineage state establish basal sialyltransferase expression and constrain the sialoglycan landscape available to tumours. We highlight emerging single-cell evidence that stromal populations, particularly cancer-associated fibroblasts, can acquire hypersialylation and actively generate immunosuppressive Siglec ligands. We also examine how transcriptional and oncogenic regulators, including SOX2, MYC, and androgen receptor signalling, reprogrammesialyltransferase expression to produce tumour-specific sialoglycan profiles. Finally, we consider how standard-of-care therapies alter both ligand availability and immune composition, thereby dynamically modifying the sialoglycan–Siglec axis during treatment and resistance. Understanding these context-dependent determinants will be critical for interpreting sialylation in cancer biology and for designing effective therapeutic strategies targeting sialoglycan–Siglec interactions.  \nIntroduction  \nAltered glycosylation is a well-established feature of cancer and contributes to multiple aspects of tumour biology, including cell signalling, adhesion, immune recognition, and metastasis [1–4]. Among these changes, aberrant sialylation is one of the most consistently observed glycan modifications in cancer. Sialic acids are terminal monosaccharides added to glycoproteins and glycolipids through the activity of sialyltransferases, and their expression at the cell surface influences interactions between tumour cells and the surrounding microenvironment [5,6] . In particular, sialylated glycans can engage sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of receptors expressed predominantly by immune cells, many of which transmit inhibitory signals that dampen immune activation [7] .  \nIncreasing evidence indicates that the sialoglycan–Siglec axis plays an important role in shaping anti-tumour immune responses. Tumour-associated hypersialylation has been shown to impair myeloid and lymphoid cell function through Siglec-mediated signalling, contributing to immune suppression within the tumour microenvironment [8–14] . However, the extent and nature of sialoglycan expression, as well as the Siglec repertoire present within tumours, vary considerably between cancer types. These  \n© 2026 The Author(s) . This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution 1 License 4 .0 (CC BY) .  \nBioscience Reports (2026) 46 BSR20250119 [https://doi.org/10.1042/BSR202","cbCaiuwp0IMof4I5","https://ap.wps.com/l/cbCaiuwp0IMof4I5","pdf",5033701,15,"English","# Introduction\n## Aberrant sialylation and Siglec-mediated immune inhibition\n## Tissue-specific glycosylation programmes and cancer-related rewiring\n## Tumour cellular heterogeneity and immune landscape dependence\n## Scope and aims of the review","[{\"question\":\"What is the sialoglycan–Siglec axis, and why is it relevant to cancer?\",\"answer\":\"The axis links tumour-associated sialylated glycans (sialoglycans) to Siglecs on immune cells. Siglec engagement often transmits inhibitory signals that suppress anti-tumour immune activity, shaping responses in the tumour microenvironment.\"},{\"question\":\"How do tissue-specific factors influence sialylation in cancer?\",\"answer\":\"Tissue-of-origin programmes and differentiation state establish basal sialyltransferase expression and constrain the sialoglycan repertoire available to tumours. This tissue context contributes to tumour-specific sialoglycan profiles.\"},{\"question\":\"How can stromal cells contribute to immunosuppressive Siglec ligands?\",\"answer\":\"Emerging single-cell evidence indicates that stromal populations, especially cancer-associated fibroblasts, can acquire hypersialylation. 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