{"title":"Siglecs: From Biomodulation to Immunotherapy.","authors":"Jia Chen, Yumin Huang, Yafei Wang, Tianlei Sun, Congcong Li, Yuan Feng, Zhenbiao Wu","doi":"10.2174/0113892037372672250605183318","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Sialic acid-binding immunoglobulin-like lectins (Siglecs) are cell-surface immunological receptors predominantly expressed on immune cells such as monocytes, macrophages, and dendritic cells. They play a crucial role in regulating inflammatory processes in various diseases and serve as immunological checkpoints in cancer. Despite several immune checkpoint inhibitors targeting Siglecs having entered clinical trials, the number of Siglec-targeted immunotherapies remains limited.</p><p><strong>Objective: </strong>This review aims to investigate the contributions of Siglecs in human diseases and explore novel therapeutic strategies targeting the Siglec-sialic acid immunological axis.</p><p><strong>Methods: </strong>The authors systematically searched PubMed, Web of Science, and Google Scholar for publications mainly from 2015-2025, using search terms related to Siglecs, tumors, autoimmune diseases, and specific Siglec subtypes (CD169, Siglec2). Studies were included if they examined Siglecs biology, immunomodulation, or immunotherapeutic potential. Studies not directly relevant to Siglecs function/therapeutics and non-peer-reviewed materials (conference abstracts, editorials) were excluded. Screening was done via titles and abstracts with data referenced from research article results, and eligible articles underwent full-text review for final inclusion.</p><p><strong>Results: </strong>The analysis reveals that Siglecs exhibit dual functions, acting as both activators and inhibitors of immune responses. They are implicated in the pathogenesis of various diseases, including cancer, autoimmune disorders, and viral infections. Several Siglec-targeted immunotherapies are currently in clinical trials, demonstrating their potential in disease management. For instance, Siglec15 and Siglec10 have been identified as potential immune checkpoints in cancer, while Siglec2 and Siglec10 play roles in autoimmune diseases like systemic lupus erythematosus (SLE).</p><p><strong>Conclusion: </strong>Siglecs are key immunomodulators that mediate cell-cell and pathogen interactions, playing pivotal roles in human diseases. Further research into their mechanisms and clinical applications is essential to fully harness their therapeutic potential. Targeting Siglecs offers promising avenues for developing novel immunotherapies, particularly in cancer and autoimmune diseases.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current protein & peptide science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0113892037372672250605183318","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are cell-surface immunological receptors predominantly expressed on immune cells such as monocytes, macrophages, and dendritic cells. They play a crucial role in regulating inflammatory processes in various diseases and serve as immunological checkpoints in cancer. Despite several immune checkpoint inhibitors targeting Siglecs having entered clinical trials, the number of Siglec-targeted immunotherapies remains limited.
Objective: This review aims to investigate the contributions of Siglecs in human diseases and explore novel therapeutic strategies targeting the Siglec-sialic acid immunological axis.
Methods: The authors systematically searched PubMed, Web of Science, and Google Scholar for publications mainly from 2015-2025, using search terms related to Siglecs, tumors, autoimmune diseases, and specific Siglec subtypes (CD169, Siglec2). Studies were included if they examined Siglecs biology, immunomodulation, or immunotherapeutic potential. Studies not directly relevant to Siglecs function/therapeutics and non-peer-reviewed materials (conference abstracts, editorials) were excluded. Screening was done via titles and abstracts with data referenced from research article results, and eligible articles underwent full-text review for final inclusion.
Results: The analysis reveals that Siglecs exhibit dual functions, acting as both activators and inhibitors of immune responses. They are implicated in the pathogenesis of various diseases, including cancer, autoimmune disorders, and viral infections. Several Siglec-targeted immunotherapies are currently in clinical trials, demonstrating their potential in disease management. For instance, Siglec15 and Siglec10 have been identified as potential immune checkpoints in cancer, while Siglec2 and Siglec10 play roles in autoimmune diseases like systemic lupus erythematosus (SLE).
Conclusion: Siglecs are key immunomodulators that mediate cell-cell and pathogen interactions, playing pivotal roles in human diseases. Further research into their mechanisms and clinical applications is essential to fully harness their therapeutic potential. Targeting Siglecs offers promising avenues for developing novel immunotherapies, particularly in cancer and autoimmune diseases.
背景：唾液酸结合免疫球蛋白样凝集素（Siglecs）是细胞表面的免疫受体，主要表达于免疫细胞，如单核细胞、巨噬细胞和树突状细胞。它们在调节各种疾病的炎症过程中起着至关重要的作用，并在癌症中充当免疫检查点。尽管几种针对Siglecs的免疫检查点抑制剂已经进入临床试验，但针对Siglecs的免疫疗法的数量仍然有限。目的：研究Siglecs在人类疾病中的作用，探索以Siglecs -唾液酸免疫轴为靶点的新型治疗策略。方法：作者系统检索PubMed、Web of Science和谷歌Scholar 2015-2025年间的出版物，检索词涉及Siglecs、肿瘤、自身免疫性疾病和特定siglecc亚型（CD169、Siglec2）。如果研究涉及Siglecs生物学、免疫调节或免疫治疗潜力，则纳入研究。排除了与Siglecs功能/治疗方法不直接相关的研究和未经同行评审的材料（会议摘要、社论）。通过引用研究文章结果的标题和摘要进行筛选，并对符合条件的文章进行全文审查以最终纳入。结果：分析表明Siglecs具有双重功能，既可以激活免疫反应，也可以抑制免疫反应。它们与各种疾病的发病机制有关，包括癌症、自身免疫性疾病和病毒感染。几种siglecl靶向免疫疗法目前正处于临床试验阶段，展示了它们在疾病管理方面的潜力。例如，Siglec15和Siglec10已被确定为癌症中的潜在免疫检查点，而Siglec2和Siglec10在系统性红斑狼疮（SLE）等自身免疫性疾病中发挥作用。结论：Siglecs是介导细胞-细胞和病原体相互作用的关键免疫调节剂，在人类疾病中起着关键作用。进一步研究其机制和临床应用对于充分利用其治疗潜力至关重要。靶向Siglecs为开发新的免疫疗法提供了有希望的途径，特别是在癌症和自身免疫性疾病中。
期刊介绍：
Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.
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