Seminars in Immunology最新文献

{"title":"The role of the complement system in the response to cytotoxic therapy","authors":"Kelly S.W. Lee ,&nbsp;Qingyang Zhang ,&nbsp;Tatsuya Suwa,&nbsp;Heather Clark,&nbsp;Monica M. Olcina","doi":"10.1016/j.smim.2024.101927","DOIUrl":"10.1016/j.smim.2024.101927","url":null,"abstract":"<div><div>The complement system is increasingly recognised as a key player in tumour progression and response to cancer treatment. Cytotoxic therapies, including chemo- and radiotherapy are standard-of-care for the majority of cancer patients. Cytotoxics have been found to alter the expression of complement system proteins and activation of components<strong>.</strong> Many recent reports highlight the role of local dysregulation of complement proteins in the tumour microenvironment and how targeting such dysregulation can have either anti- or pro-tumoricidal effects depending on several factors including treatment scheduling, the tumour type and its microenvironment characteristics. This review will explore the complex effects of cytotoxic therapy on complement regulation and what lessons can be learnt to identify the most effective way to therapeutically modulate complement system proteins for cancer therapy.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101927"},"PeriodicalIF":7.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing complement activation by therapeutic anti-tumor antibodies: Mechanisms, strategies, and engineering approaches","authors":"Vitalijs Ovcinnikovs ,&nbsp;Karin Dijkman ,&nbsp;Gijs G. Zom ,&nbsp;Frank J. Beurskens ,&nbsp;Leendert A. Trouw","doi":"10.1016/j.smim.2024.101922","DOIUrl":"10.1016/j.smim.2024.101922","url":null,"abstract":"<div><div>The complement system plays an integral role in both innate and adaptive immune responses. Beyond its protective function against infections, complement is also known to influence tumor immunity, where its activation can either promote tumor progression or mediate tumor cell destruction, depending on the context. One such context can be provided by antibodies, with their inherent capacity to activate the classical complement pathway. In recent years, our understanding of the mechanisms governing complement activation by IgG and IgM antibodies has expanded significantly. At the same time, preclinical and clinical studies on antibodies such as rituximab, ofatumumab, and daratumumab have provided evidence for the role of complement in therapeutic success, encouraging strategies to further enhance its activity. In this review we examine the main determinants of antibody-mediated complement activation, highlighting the importance of antibody subclass, affinity, valency, and geometry of antigen engagement. We summarize the evidence for complement involvement in anti-tumor activity and challenges of accurately estimating the extent of its contribution to therapeutic efficacy. Furthermore, we explore several engineering approaches designed to enhance complement activation, including increased Fc oligomerization and C1q affinity, bispecific C1q-recruiting antibodies, IgG subclass chimeras, as well as antibody and paratope combinations. Strategies targeting membrane-bound complement regulatory proteins to overcome tumor-associated complement inhibition are also discussed as a method to boost therapeutic efficacy. Finally, we highlight the potential of complement-dependent cellular cytotoxicity (CDCC) and complement-dependent cellular phagocytosis (CDCP) as effector mechanisms that warrant deeper investigation.</div><div>By integrating advances in antibody and complement biology with insights from efforts to enhance complement activation in therapeutic antibodies, this review aims to provide a comprehensive framework of antibody design and engineering strategies that optimize complement activity for improved anti-tumor efficacy.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101922"},"PeriodicalIF":7.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the multifaceted roles of galectins in self-defense","authors":"Sachiko Sato ,&nbsp;Jun Iwaki ,&nbsp;Jun Hirabayashi","doi":"10.1016/j.smim.2024.101926","DOIUrl":"10.1016/j.smim.2024.101926","url":null,"abstract":"<div><div>In this review, we aim to explore the multifaceted roles of galectins in host defense from a broader perspective, particularly regarding their functions when host integrity is compromised. Numerous comprehensive reviews on galectin functions in immunity have already been published. For researchers new to the field, this wealth of information may create an impression of galectins as proteins involved in a wide array of biological processes. Furthermore, due to the heterogeneity of galectin ligands, glycans, there is a risk of perceiving galectin-specific functions as ambiguous, potentially obscuring their core biological significance. To address this, we revisit foundational aspects, focusing on the significance of the recognition of galactose, a “late-comer” monosaccharide in evolutionary terms, provide an overview of galectin glycan binding specificity, with emphasis on the potential biological importance of each carbohydrate-recognition domain. We also discuss the biological implications of the galectin location paradox wherein these cytosolic lectins function in host defense despite their glycan ligands being synthesized in the secretory pathway. Additionally, we examine the role of galectins in liquid-liquid phase separation on membranes, which may facilitate their diverse functions in cellular responses. Through this approach, we aim to re-evaluate the complex and diverse biological roles of galectins in host defense.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101926"},"PeriodicalIF":7.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles for Siglec-glycan interactions in regulating immune cells","authors":"Sung-Yao Lin ,&nbsp;Edward N. Schmidt ,&nbsp;Kei Takahashi-Yamashiro ,&nbsp;Matthew S. Macauley","doi":"10.1016/j.smim.2024.101925","DOIUrl":"10.1016/j.smim.2024.101925","url":null,"abstract":"<div><div>Cell surface complex carbohydrates, known as glycans, are positioned to be the first point of contact between two cells. Indeed, interactions between glycans with glycan-binding can modulate cell-cell interactions. This concept is particularly relevant for immune cells, which use an array of glycan-binding proteins to help in the process of differentiating ‘self’ from ‘non-self’. This is exemplified by the sialic acid-binding immunoglobulin-type lectins (Siglecs), which recognize sialic acid. Given that sialic acid is relatively unique to vertebrates, immune cells leverage Siglecs to recognize sialic acid as a marker of ‘self’. Siglecs serve many biological roles, with most of these functions regulated through interactions with their sialoglycan ligands. In this review, we provide a comprehensive update on the ligands of Siglecs and how Siglec-sialoglycan interactions help regulate immune cells in the adaptive and innate immune system.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101925"},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The complement system in clinical oncology: Applications, limitations and challenges","authors":"Daniel Ajona ,&nbsp;Mark S. Cragg ,&nbsp;Ruben Pio","doi":"10.1016/j.smim.2024.101921","DOIUrl":"10.1016/j.smim.2024.101921","url":null,"abstract":"<div><div>The complement system, a key component of innate immunity, is involved in seemingly contradictory aspects of tumor progression and cancer therapy. It can act as an immune effector against cancer and modulate the antitumor activity of certain therapeutic antibodies, but it can also contribute to a tumor-promoting microenvironment. Understanding this dual role should lead to the development of better therapeutic tools, strategies for cancer treatment and biomarkers for the clinical management of cancer patients. Here, we review recent advances in the understanding of the role of complement in cancer, focusing on how these findings are being translated into the clinic. We highlight the activity of therapeutic agents that modulate the complement system, as well as combination therapies that integrate complement modulation with existing therapies. We conclude that the role of complement activation in cancer is a rapidly evolving field with the potential to translate findings into new therapeutic strategies and clinically useful biomarkers</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101921"},"PeriodicalIF":7.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement regulation in tumor immune evasion","authors":"Guijun Liu ,&nbsp;Xuxiao He ,&nbsp;Gaoxiang Zhao ,&nbsp;Zhimin Lu","doi":"10.1016/j.smim.2024.101912","DOIUrl":"10.1016/j.smim.2024.101912","url":null,"abstract":"<div><div>The complement system plays crucial roles in both innate and adaptive immune responses, facilitating the elimination of pathogens such as microorganisms and damaged cells, including cancer cells. It is tightly regulated and integrated with cell-mediated immunity. In the tumor microenvironment, the complement system performs both immune and nonimmune functions in tumor and immune cells through pathways that depend on or are independent of complement activation, thereby promoting immune evasion and tumor progression.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101912"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs","authors":"Eleonora Nardini ,&nbsp;Ernesto Rodriguez ,&nbsp;Yvette van Kooyk","doi":"10.1016/j.smim.2024.101913","DOIUrl":"10.1016/j.smim.2024.101913","url":null,"abstract":"<div><div>The immune system is a complex network of highly specialized microenvironments, denominated niches, which arise from dynamic interactions between immune and parenchymal cells as well as acellular components such as structural elements and local molecular signals. A critical, yet underexplored, layer shaping these niches is the glycome, the complete repertoire of glycans and glycoconjugates produced by cells. The glycome is prevalent in the outer membrane of cells and their secreted components, and can be sensed by glycan binding receptors on immune cells. These receptors detect changes in glycosylation and consequently modulate immune cell activity, trafficking, and signalling, altering homeostasis. Tissues like the brain and the placenta are prone to accommodate tolerance, while the gut and the thymus are sensitive to inflammation. We provide here an overview of current literature that shows the impact of altered glycosylation of tissues on host immune cells and how interference in this process may lead to new diagnostics and immune therapeutics, aiming to restore the immune balance in autoimmunity and cancer.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101913"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galectins and Host–Pathogen Interactions: The roles in viral infections","authors":"Sheng-Fang Wang ,&nbsp;Hung-Lin Chen ,&nbsp;Fu-Tong Liu","doi":"10.1016/j.smim.2024.101911","DOIUrl":"10.1016/j.smim.2024.101911","url":null,"abstract":"<div><div>Galectins, a family of carbohydrate-binding proteins, play crucial roles in the host–virus interaction landscape. This review explores the multifaceted contributions of endogenous galectins to various stages of the viral lifecycle, including attachment, replication, assembly, and release of progeny virions. Recent studies have indicated that viral infections can induce the expression and secretion of specific galectins, with elucidated signaling pathways in some cases, enhancing our understanding of their regulatory mechanisms. While many studies have focused on the effects of exogenous recombinant galectins, there is growing interest in the intrinsic functions of endogenous galectins, particularly through genetic alterations in cellular models. This review highlights the need for further research to uncover the complex roles of galectins in modulating viral infections and emphasizes their potential as therapeutic targets in the fight against viral diseases. Understanding these interactions could pave the way for novel strategies to enhance host defense mechanisms and mitigate viral pathogenesis.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"76 ","pages":"Article 101911"},"PeriodicalIF":7.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABO blood groups and galectins: Implications in transfusion medicine and innate immunity","authors":"Connie M. Arthur ,&nbsp;Marie Hollenhorst ,&nbsp;Shang-Chuen Wu ,&nbsp;Ryan Jajosky ,&nbsp;Hirotomo Nakahara ,&nbsp;Hau-Ming Jan ,&nbsp;Leon Zheng ,&nbsp;Mischa Covington ,&nbsp;Seth Rakoff-Nahoum ,&nbsp;Melissa Yeung ,&nbsp;William Lane ,&nbsp;Cassandra Josephson ,&nbsp;Richard D. Cummings ,&nbsp;Sean R. Stowell","doi":"10.1016/j.smim.2024.101892","DOIUrl":"10.1016/j.smim.2024.101892","url":null,"abstract":"<div><div>ABO blood group antigens, which are complex carbohydrate moieties, and the first human polymorphisms identified, are critical in transfusion medicine and transplantation. Despite their discovery over a century ago, significant questions remain about the development of anti-ABO antibodies and the structural features of ABO antigens that cause hemolytic transfusion reactions. Anti-ABO antibodies develop naturally during the first few months of life, in contrast to other red blood cell (RBC) alloantibodies which form after allogeneic RBC exposure. Anti-ABO antibodies are the most common immune barrier to transfusion and transplantation, but the factors driving their formation are incompletely understood. Some studies suggest that microbes that express glycans similar in structure to the blood group antigens could play a role in anti-blood group antibody formation. While the role of these microbes in clinically relevant anti-blood group antibody formation remains to be defined, the presence of these microbes raises questions about how blood group-positive individuals protect themselves against blood group molecular mimicry. Recent studies suggest that galectins can bind and kill microbes that mimic blood group antigens, suggesting a unique host defense mechanism against microbial molecular mimicry. However, new models are needed to fully define the impact of microbes, galectins, or other factors on the development of clinically relevant naturally occurring anti-blood group antibodies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101892"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NGS data analysis for molecular diagnosis of Inborn Errors of Immunity","authors":"XT Yang,&nbsp;WL Yang,&nbsp;YL Lau","doi":"10.1016/j.smim.2024.101901","DOIUrl":"10.1016/j.smim.2024.101901","url":null,"abstract":"<div><div>Inborn errors of immunity (IEI) encompass a group of disorders with a strong genetic component. Prompt and accurate diagnosis of these disorders is essential for effective clinical management. Next-generation sequencing (NGS) has significantly enhanced the diagnostic process by offering a comprehensive and scalable approach for identifying genomic variations causal for these disorders. Nevertheless, the bioinformatics analysis of NGS data poses several challenges. In this review, we explore these challenges and share our insights on addressing them, aiming to improve the overall diagnostic yield.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101901"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}