Seminars in Immunology最新文献_第2页

Chimeric antigen receptor therapy for hepatocellular carcinoma 嵌合抗原受体治疗肝细胞癌

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2026-03-10 DOI: 10.1016/j.smim.2025.102000

Lorenz Kocheise , Mohamed-Reda Benmebarek , Mitchell Ho , Tim F. Greten

{"title":"Chimeric antigen receptor therapy for hepatocellular carcinoma","authors":"Lorenz Kocheise , Mohamed-Reda Benmebarek , Mitchell Ho , Tim F. Greten","doi":"10.1016/j.smim.2025.102000","DOIUrl":"10.1016/j.smim.2025.102000","url":null,"abstract":"<div><div>Adapting the success of chimeric antigen receptor T cell therapy from hematologic malignancies to solid tumors has become a major focus of ongoing research activities. However, the unique challenges posed by solid tumors, such as limited immune cell infiltration, reduced T cell persistence, and antigen loss, have led to only limited success in early clinical trials. Recently, combinatorial strategies incorporating next-generation armored CAR T cells along with various alternative immune cell types have rekindled optimism in the field. Hepatocellular carcinoma represents a distinct entity due to the unique characteristics of the liver microenvironment, including the influence of lipid metabolism, bile acids, and microbial compounds from the gut-liver axis. Furthermore, HCC is characterized by a variety of tumor-specific and tumor-associated antigens, enabling targeted approaches with minimal risk of on-target/off-tumor effects. The unique complexity of HCC, along with the underlying liver diseases that give rise to these tumors, presents both challenges and opportunities for cellular therapies. In this review, we examine the current landscape of CAR T cell therapy for HCC, highlighting recent clinical and preclinical developments. Furthermore, we discuss why HCC may be especially well-suited for tailored CAR-based strategies, given the liver’s specific anatomical and immunological properties.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"81 ","pages":"Article 102000"},"PeriodicalIF":7.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395438","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

Editorial: Autoimmune diseases of the central nervous system 社论：中枢神经系统的自身免疫性疾病。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2026-02-21 DOI: 10.1016/j.smim.2026.102018

Simone Mader, Markus Reindl

引用次数: 0

New insights into Th9 cells in inflammatory bowel diseases 炎症性肠病中Th9细胞的新认识

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2025-12-16 DOI: 10.1016/j.smim.2025.102013

Markus F. Neurath

引用次数: 0

IL-1 family members as regulators of lymphoid type-2 immunity in cancer IL-1家族成员在癌症中作为淋巴2型免疫的调节因子

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2025-11-28 DOI: 10.1016/j.smim.2025.102005

Stefania Roma , Filippo Colombo , Lucia De Monte , Maria Pia Protti

{"title":"IL-1 family members as regulators of lymphoid type-2 immunity in cancer","authors":"Stefania Roma , Filippo Colombo , Lucia De Monte , Maria Pia Protti","doi":"10.1016/j.smim.2025.102005","DOIUrl":"10.1016/j.smim.2025.102005","url":null,"abstract":"<div><div>IL-1 family members, such as IL-1 and IL-33, are present in the tumor microenvironment and exert tumor-intrinsic and tumor-extrinsic functions with both pro- and anti-tumor effects. Among their immunoregulatory roles, both cytokines contribute to lymphoid type-2 immunity. IL-1 can indirectly promote CD4<sup>+</sup> Th2 responses by inducing thymic stromal lymphopoietin production by tumor cells or cancer associated fibroblasts that conditions Th2-polarizing dendritic cells, whereas IL-33 is a potent direct activator of CD4<sup>+</sup> Th2 and other type-2 immune cells, such as group 2 innate lymphoid cells (ILC2s). In a large majority of established human cancers, CD4<sup>+</sup> Th2 cell responses correlate with tumor-promotion, whereas expansion of ILC2s can either suppress or promote tumor immunity in a more balanced way, leading to tumor progression or regression. Interestingly, the two prototypical Th2 cytokines IL-13 and IL-5 exert apparently pro- and anti-tumor opposing functions by recruitment of myeloid-derived cells and eosinophils, respectively. In addition, anti-tumor ILC2s under the influence of the tumor microenvironment may become dysfunctional, ultimately resulting in tumor-progression. Understanding the specific cancer context and considering the similarities as well as the distinctive features of the two lymphoid type-2 cell subsets is essential for developing effective immunotherapeutic strategies by targeting the IL-1 and IL-33 cytokines.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"81 ","pages":"Article 102005"},"PeriodicalIF":7.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624799","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

Therapeutic immune tolerance for central nervous system autoimmune diseases – Prospects, challenges and pitfalls 中枢神经系统自身免疫性疾病的治疗性免疫耐受-前景、挑战和缺陷。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2026-02-11 DOI: 10.1016/j.smim.2026.102016

Andreas Lutterotti , Roland Martin

{"title":"Therapeutic immune tolerance for central nervous system autoimmune diseases – Prospects, challenges and pitfalls","authors":"Andreas Lutterotti , Roland Martin","doi":"10.1016/j.smim.2026.102016","DOIUrl":"10.1016/j.smim.2026.102016","url":null,"abstract":"<div><div>Autoimmune diseases of the central nervous system (CNS), including multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), are characterized by chronic inflammation driven by autoreactive immune responses against CNS antigens. Successes in the development of efficacious immunotherapies are hampered by the risks of broad immunosuppression and the consequences of compromising physiological immune functions. Antigen-specific immune tolerance offers a promising alternative by selectively silencing pathogenic immune responses while preserving global immune competence. Advances in understanding of pathophysiology and target antigens in multiple sclerosis, neuromyleitis optica spectrum disroders (NMOSD) myelin oligondendrocyte protein (MOG) antibody associated disease (MOGAD) have enabled the development of antigen-based tolerization strategies. These approaches primarily act through restoration of peripheral tolerance via modulation of autoreactive T and B cell responses. Clinical trials in MS and NMOSD have provided critical insights into key challenges of translation and clinical development, including optimal antigen selection, route of administration, patient stratification and trial design constraints. Future progress in MS, NMO and MOGAD will also depend on precise characterization of immunodominant epitopes and the development of standardized biomarkers of tolerance induction and their integration in novel trial designs. Successful induction of durable, antigen-specific immune tolerance would represent a paradigm shift in treating CNS autoimmunity, enabling disease-specific, safe, and sustained remission without generalized immunosuppression.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"81 ","pages":"Article 102016"},"PeriodicalIF":7.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183158","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 role of non-cancer cell infections in oncolytic virus therapy 非癌细胞感染在溶瘤病毒治疗中的作用。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI: 10.1016/j.smim.2025.101998

Jahanara Rajwani , Douglas J. Mahoney

{"title":"The role of non-cancer cell infections in oncolytic virus therapy","authors":"Jahanara Rajwani , Douglas J. Mahoney","doi":"10.1016/j.smim.2025.101998","DOIUrl":"10.1016/j.smim.2025.101998","url":null,"abstract":"<div><div>Oncolytic viruses (OV) are designed to seek out and kill cancer cells, while simultaneously inciting potent antitumour immunity. While their exact mechanism of action is incompletely understood, therapeutic activity is proposed to rely on viruses selectively infecting cancer cells – not only to debulk the tumour, but also to elicit immunogenic cell death (ICD) of cancer cells and subsequent antigen-specific immunity. However, despite being engineered for cancer cell selectivity, several studies have demonstrated OV-induced antitumour activity against tumours that do not robustly support virus infection <em>in vivo</em>. Further, many non-malignant cells within, and outside of, the tumour microenvironment (TME) have been shown to support OV infection, and in some cases, contribute to tumour regression. These unexpected findings warrant a more comprehensive understanding of the mechanisms by which OV-infected non-cancer cells elicit antitumour activity. Thus, in this review, we aim to summarize current knowledge on the role of non-cancer cell infections in OV therapy. We focus our attention primarily on infected non-cancer cells in the TME, including endothelial cells, fibroblasts and perivascular cells, as well as those in secondary lymphoid organs (spleen and lymph nodes). In addition, we include a brief commentary on the impact of liver and peripheral blood mononuclear cell infections. Interestingly, while the consequences of some non-malignant cell infections appear to be similar across multiple OVs, the outcome of other infections are OV-specific. This highlights the need to better understand cellular infections for each OV, in order to leverage this information for the development of next generation OV platforms.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"81 ","pages":"Article 101998"},"PeriodicalIF":7.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670429","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

Emerging roles of IL-9 and Th9 cells in respiratory viral illnesses IL-9和Th9细胞在呼吸道病毒性疾病中的新作用。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-03-01 Epub Date: 2026-02-24 DOI: 10.1016/j.smim.2026.102017

Jyotsna Dandotiya , Srikanth Sadhu , Rucha R. Chandwaskar , Amit Awasthi

{"title":"Emerging roles of IL-9 and Th9 cells in respiratory viral illnesses","authors":"Jyotsna Dandotiya , Srikanth Sadhu , Rucha R. Chandwaskar , Amit Awasthi","doi":"10.1016/j.smim.2026.102017","DOIUrl":"10.1016/j.smim.2026.102017","url":null,"abstract":"<div><div>Upon antigenic stimulation and cytokine cues, CD4⁺ T cells differentiate into specialized helper subsets, giving rise to Th1, Th2, Th9 and Th17 cell lineages. These subsets orchestrate distinct immune functions that protect the host but can also drive immunopathology when dysregulated. The classical Th1–Th2 paradigm expanded with the discovery of Th17 and Th9 cells, revealing greater diversity and complexity in Th cell biology. Th9 cells<strong>,</strong> generated under the influence of TGF-β and IL-4, are defined by robust production of interleukin-9 (IL-9). IL-9 is now recognized as a multifunctional mediator produced by Th9 cells, mast cells, ILC2s, Tregs and certain Th17 subsets. Fate-mapping and reporter mouse models have improved our understanding of IL-9–producing immunocytes, though limitations remain in defining temporal and tissue-specific dynamics. As shown earlier, IL-9 promotes mastcell proliferation, mucus hypersecretion, epithelial changes and airway remodelling in allergic inflammation and asthma. Genetic studies have linked IL-9/IL-9 receptor variants to increased susceptibility to allergic diseases such as asthma. Similarly, during respiratory viral infections, including RSV and COVID-19, IL-9 amplifies type 2 inflammation, granulocyte recruitment and mucus production, exacerbating airway obstruction. In fact, emerging evidence implicates a Foxo1-IL-9 axis in COVID-19, where IL-9 enhances lung inflammation and impairs antiviral interferon-stimulated gene responses. Collectively, IL-9 represents a context-dependent driver of virus-induced lung pathology and a promising therapeutic target requiring deeper mechanistic and translational investigation.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"81 ","pages":"Article 102017"},"PeriodicalIF":7.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147312076","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

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2026-01-01

引用次数: 0

TH9 cells and interleukin-9 in parasitic infections: Updates, opportunities, and challenges 寄生虫感染中的TH9细胞和白细胞介素-9：最新进展、机遇和挑战

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2025-12-01 Epub Date: 2025-11-01 DOI: 10.1016/j.smim.2025.102003

Javier Orozco-Cordoba, Cleofas Marcial-Medina, Paula Licona-Limón

{"title":"TH9 cells and interleukin-9 in parasitic infections: Updates, opportunities, and challenges","authors":"Javier Orozco-Cordoba, Cleofas Marcial-Medina, Paula Licona-Limón","doi":"10.1016/j.smim.2025.102003","DOIUrl":"10.1016/j.smim.2025.102003","url":null,"abstract":"<div><div>Over the past decades, Interleukin-9 (IL-9) and T<sub>H</sub>9 cells, have gained attention as important regulators of diverse responses throughout the promotion of activation and expansion of diverse cell subtypes. T<sub>H</sub>9 cells have been studied in several immunological contexts, including allergic and autoimmune responses, cancer and infectious diseases; being the latest one, specifically those induced by parasites, the main focus of this review. T<sub>H</sub>9 cells have risen as critical mediators of the immune response against parasites, including roundworms, flatworms, tapeworms, and hookworms; however, the number of parasitic diseases influenced by this cell subset was still limited in studies published up to 2016. In this review, we aimed to summarize the latest findings regarding the roles of T<sub>H</sub>9 cells and IL-9 in parasitic infections, seeking to provide a comprehensive overview of latest knowledge in the field including the models of parasites never studied. We compile recent evidence highlighting both protective and pathogenic roles for IL-9, discuss the challenges to unravel the complexity of T<sub>H</sub>9-IL-9 mediated responses during parasitic infections, as well as the opportunities for therapeutic intervention that will help to translate new findings into future clinical applications.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"80 ","pages":"Article 102003"},"PeriodicalIF":7.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416831","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

Reovirus oncolysis and the next frontiers for this unique oncoviral immunotherapy 呼肠孤病毒溶瘤和这种独特的肿瘤病毒免疫疗法的下一个前沿。

IF 7.8 2区医学

Seminars in Immunology Pub Date : 2025-12-01 Epub Date: 2025-09-30 DOI: 10.1016/j.smim.2025.101995

Negar Sharifi , Amir Emamie , Nastaran Rafiee , Salar Pashangzadeh , Eknoor Walia , Nikolas Tim Martin , Huy-Dung Hoang , Xiao Xiang , Tommy Alain

{"title":"Reovirus oncolysis and the next frontiers for this unique oncoviral immunotherapy","authors":"Negar Sharifi , Amir Emamie , Nastaran Rafiee , Salar Pashangzadeh , Eknoor Walia , Nikolas Tim Martin , Huy-Dung Hoang , Xiao Xiang , Tommy Alain","doi":"10.1016/j.smim.2025.101995","DOIUrl":"10.1016/j.smim.2025.101995","url":null,"abstract":"<div><div>Reovirus is one of the most clinically investigated oncolytic viruses, with over 50 clinical trials and more than 1700 patients treated to date. Although it has yet to achieve complete regulatory approval, reovirus remains a promising oncolytic virus candidate for cancer immunotherapy due to its preferential replication in malignant cells, minimal toxicity in normal tissues, availability to be delivered via multiple routes, and strong immunostimulatory properties. As a non-enveloped, double-stranded RNA virus of the <em>Reoviridae</em> family, reovirus is typically asymptomatic in healthy individuals unlike its pathogenic relative, rotavirus, thus making it especially attractive for clinical use. Recent research has significantly expanded its therapeutic potential beyond direct oncolysis, highlighting its ability to remodel the tumor microenvironment, activate both innate and adaptive immunity, and synergize with chemotherapy, radiotherapy, and immune checkpoint inhibitors. Moreover, advances in oral delivery, nanoparticle encapsulation, mesenchymal stem cell-mediated transport, and genetic engineering, have further enhanced its safety, targeting precision, and therapeutic efficacy. This review summarizes recent breakthroughs in reovirus-based virotherapy and explores emerging strategies that may unlock its full potential as a next-generation immunotherapeutic platform.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"80 ","pages":"Article 101995"},"PeriodicalIF":7.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207731","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