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Complement regulators as novel targets for anti-cancer therapy: A comprehensive review 补体调节因子作为抗癌治疗的新靶点：综述
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2025-03-01 Epub Date: 2025-01-18 DOI: 10.1016/j.smim.2025.101931
Ruchi Saxena , Elizabeth B. Gottlin , Michael J. Campa , You-Wen He , Edward F. Patz Jr.
{"title":"Complement regulators as novel targets for anti-cancer therapy: A comprehensive review","authors":"Ruchi Saxena ,&nbsp;Elizabeth B. Gottlin ,&nbsp;Michael J. Campa ,&nbsp;You-Wen He ,&nbsp;Edward F. Patz Jr.","doi":"10.1016/j.smim.2025.101931","DOIUrl":"10.1016/j.smim.2025.101931","url":null,"abstract":"<div><div>Cancer remains a formidable global health challenge requiring the continued exploration of innovative therapeutic approaches. While traditional treatment strategies including surgery, chemotherapy, and radiation therapy have had some success, primarily in early-stage disease, the quest for more targeted, personalized, safer, and effective therapies remains an ongoing pursuit. Over the past decade, significant advances in the field of tumor immunology have dramatically shifted a focus towards immunotherapy, although the ability to harness and coopt the immune system to treat cancer is still just beginning to be realized. One important area that has yet to be fully explored is the complement system, an integral part of innate immunity that has gathered attention recently as a source of potential targets for anti-cancer therapy. The complement system has a complex and context dependent role in cancer biology in that it not only contributes to immune surveillance but also may promote tumor progression. Complement regulators, including CD46, CD55, CD59, and complement factor H, exercise defined control over complement activation, and have also been acknowledged for their role in the tumor microenvironment. This review explores the intricate role of complement regulators in cancer development and progression, examining their potential as therapeutic targets, current strategies, challenges, and the evolving landscape of clinical research.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101931"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014955","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}
引用次数: 0
Learning from Inborn Errors of Immunity: From mechanisms to translation 从先天性免疫错误中学习：从机制到转化。
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2025-03-01 Epub Date: 2025-01-11 DOI: 10.1016/j.smim.2025.101932
Mohamed-Ridha Barbouche, Luigi D. Notarangelo
{"title":"Learning from Inborn Errors of Immunity: From mechanisms to translation","authors":"Mohamed-Ridha Barbouche,&nbsp;Luigi D. Notarangelo","doi":"10.1016/j.smim.2025.101932","DOIUrl":"10.1016/j.smim.2025.101932","url":null,"abstract":"","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101932"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972901","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}
引用次数: 0
Beyond the Norm: The emerging interplay of complement system and extracellular matrix in the tumor microenvironment 超常：肿瘤微环境中补体系统和细胞外基质的相互作用。
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2025-03-01 Epub Date: 2025-01-09 DOI: 10.1016/j.smim.2025.101929
Andrea Balduit , Chiara Agostinis , Roberta Bulla
{"title":"Beyond the Norm: The emerging interplay of complement system and extracellular matrix in the tumor microenvironment","authors":"Andrea Balduit ,&nbsp;Chiara Agostinis ,&nbsp;Roberta Bulla","doi":"10.1016/j.smim.2025.101929","DOIUrl":"10.1016/j.smim.2025.101929","url":null,"abstract":"<div><div>Ground-breaking awareness has been reached about the intricate and dynamic connection between developing tumors and the host immune system. Being a powerful arm of innate immunity and a functional bridge with adaptive immunity, the complement system (C) has also emerged as a pivotal player in the tumor microenvironment (TME). Its “double-edged sword” role in cancer can find an explanation in the controversial relationship between C capability to mediate tumor cell cytolysis or, conversely, to sustain chronic inflammation and tumor progression by enhancing cell invasion, angiogenesis, and metastasis to distant organs. However, comprehensive knowledge about the actual role of C in cancer progression is impaired by several limitations of the currently available studies.</div><div>In the current review, we aim to bring a fresh eye to the controversial role of C in cancer by analyzing the interplay between C and extracellular matrix (ECM) components as potential orchestrators of the TME. The interaction of C components with specific ECM components can determine C activation or inhibition and promote specific non-canonical functions, which can, in the tumor context, favor or limit progression based on the cancer setting. An in-depth and tumor-specific characterization of TME composition in terms of C components and ECM proteins could be essential to determine their potential interactions and become a key element for improving drug development, prognosis, and therapy response prediction in solid tumors.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"77 ","pages":"Article 101929"},"PeriodicalIF":7.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967200","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}
引用次数: 0
The role of the complement system in the response to cytotoxic therapy 补体系统在细胞毒性治疗反应中的作用
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2025-03-01 Epub Date: 2025-01-06 DOI: 10.1016/j.smim.2024.101927
Kelly S.W. Lee , Qingyang Zhang , Tatsuya Suwa, Heather Clark, Monica M. Olcina
{"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":"2025-03-01","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}
引用次数: 0
Complement regulation in tumor immune evasion 肿瘤免疫逃避中的补体调节。
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-11-01 Epub Date: 2024-11-22 DOI: 10.1016/j.smim.2024.101912
Guijun Liu , Xuxiao He , Gaoxiang Zhao , Zhimin Lu
{"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}
引用次数: 0
The tissue glycome as regulator of immune activation and tolerance mediated by C-type lectins and Siglecs 由 C 型凝集素和 Siglecs 介导的组织糖蛋白是免疫激活和耐受的调节器
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-11-01 Epub Date: 2024-11-27 DOI: 10.1016/j.smim.2024.101913
Eleonora Nardini , Ernesto Rodriguez , Yvette van Kooyk
{"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}
引用次数: 0
Galectins and Host–Pathogen Interactions: The roles in viral infections Galectins 和宿主-病原体相互作用：在病毒感染中的作用
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-11-01 Epub Date: 2024-11-23 DOI: 10.1016/j.smim.2024.101911
Sheng-Fang Wang , Hung-Lin Chen , Fu-Tong Liu
{"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}
引用次数: 0
NGS data analysis for molecular diagnosis of Inborn Errors of Immunity 用于先天性免疫错误分子诊断的 NGS 数据分析
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-07-01 Epub Date: 2024-11-06 DOI: 10.1016/j.smim.2024.101901
XT Yang, WL Yang, YL Lau
{"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}
引用次数: 0
ABO blood groups and galectins: Implications in transfusion medicine and innate immunity ABO 血型和半凝血酶：输血医学和先天免疫的意义
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-07-01 Epub Date: 2024-10-14 DOI: 10.1016/j.smim.2024.101892
Connie M. Arthur , Marie Hollenhorst , Shang-Chuen Wu , Ryan Jajosky , Hirotomo Nakahara , Hau-Ming Jan , Leon Zheng , Mischa Covington , Seth Rakoff-Nahoum , Melissa Yeung , William Lane , Cassandra Josephson , Richard D. Cummings , Sean R. Stowell
{"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}
引用次数: 0
Sialic acid and Siglec receptors in tumor immunity and immunotherapy 肿瘤免疫和免疫疗法中的 Sialic acid 和 Siglec 受体。
IF 7.4 2区 医学
Seminars in Immunology Pub Date : 2024-07-01 Epub Date: 2024-10-19 DOI: 10.1016/j.smim.2024.101893
Natalia Rodrigues Mantuano , Heinz Läubli
{"title":"Sialic acid and Siglec receptors in tumor immunity and immunotherapy","authors":"Natalia Rodrigues Mantuano ,&nbsp;Heinz Läubli","doi":"10.1016/j.smim.2024.101893","DOIUrl":"10.1016/j.smim.2024.101893","url":null,"abstract":"<div><div>Immunotherapy, including immune checkpoint inhibition, has transformed cancer therapy in recent years, providing new and potentially curative options for patients with even advanced disease. However, only a minority of patients achieve long-lasting remissions, and resistance to immune checkpoint inhibition is common. Recently, the sialic acid-Siglec axis has been proposed as a new immune checkpoint that could overcome resistance to current immunotherapy options. In this review, we summarize the current preclinical knowledge about the role of the sialic acid-Siglec interaction in immune suppression in cancer and discuss potential approaches to block this inhibitory pathway to enhance anti-cancer immunity.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"74 ","pages":"Article 101893"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479023","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}
引用次数: 0
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