Seminars in Immunology最新文献

英文中文

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 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-12-02 DOI: 10.1016/j.smim.2025.101998

Jahanara Rajwani , Douglas J. Mahoney

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 in vivo. 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.

溶瘤病毒（OV）被设计用来寻找和杀死癌细胞，同时激发有效的抗肿瘤免疫。虽然它们的确切作用机制尚不完全清楚，但有人提出，治疗活性依赖于病毒选择性地感染癌细胞——不仅可以使肿瘤脱落，还可以引起癌细胞的免疫原性细胞死亡（ICD）和随后的抗原特异性免疫。然而，尽管被设计为癌细胞选择性，一些研究已经证明ov诱导的抗肿瘤活性针对体内不支持病毒感染的肿瘤。此外，肿瘤微环境（TME）内外的许多非恶性细胞已被证明支持OV感染，在某些情况下，有助于肿瘤消退。这些意想不到的发现为更全面地了解ov感染的非癌细胞引发抗肿瘤活性的机制提供了依据。因此，在这篇综述中，我们旨在总结非癌细胞感染在OV治疗中的作用。我们主要关注TME中感染的非癌细胞，包括内皮细胞、成纤维细胞和血管周围细胞，以及次要淋巴器官（脾脏和淋巴结）中的细胞。此外，我们还包括对肝脏和外周血单核细胞感染的影响的简要评论。有趣的是，虽然一些非恶性细胞感染的结果在多个OVs中似乎是相似的，但其他感染的结果是ov特异性的。这凸显了更好地了解每种OV的细胞感染的必要性，以便利用这些信息开发下一代OV平台。

{"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":"2025-12-02","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

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 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-11-28 DOI: 10.1016/j.smim.2025.102005

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

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⁺ 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⁺ Th2 and other type-2 immune cells, such as group 2 innate lymphoid cells (ILC2s). In a large majority of established human cancers, CD4⁺ 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.

IL-1家族成员，如IL-1和IL-33，存在于肿瘤微环境中，发挥肿瘤内源性和肿瘤外源性功能，具有促肿瘤和抗肿瘤作用。在它们的免疫调节作用中，这两种细胞因子都有助于淋巴细胞2型免疫。IL-1可以通过诱导肿瘤细胞或肿瘤相关成纤维细胞产生胸腺基质淋巴生成素间接促进CD4+ Th2反应，而IL-33是CD4+ Th2和其他2型免疫细胞（如2组先天淋巴样细胞（ILC2s））的有效直接激活剂。在大多数已确定的人类癌症中，CD4+ Th2细胞反应与肿瘤促进相关，而ILC2s的扩增可以以更平衡的方式抑制或促进肿瘤免疫，导致肿瘤进展或消退。有趣的是，两种典型的Th2细胞因子IL-13和IL-5分别通过募集髓源性细胞和嗜酸性粒细胞发挥明显的促肿瘤和抗肿瘤作用。此外，抗肿瘤ILC2s在肿瘤微环境的影响下可能功能失调，最终导致肿瘤进展。了解特定的癌症背景，考虑两种淋巴样2型细胞亚群的相似性和独特特征，对于开发针对IL-1和IL-33细胞因子的有效免疫治疗策略至关重要。

{"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":"2025-11-28","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

HBV antigen as a tumour antigen in adoptive TCR-T cell therapy for HBV-related HCC: rationale and clinical effectiveness HBV抗原作为肿瘤抗原在HBV相关HCC过继TCR-T细胞治疗中的作用：理论基础和临床效果

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-11-06 DOI: 10.1016/j.smim.2025.102004

Shan He, Anthony T. Tan, Antonio Bertoletti

Hepatocellular carcinoma developing in patients with HBV chronic infection are marked by expression of whole or partial HBV antigens through a highly tissue-specific process, determined by the hepatotropism of HBV. HBV antigens are therefore a possible target for adoptive T cell immunotherapy as their expression and, consequently, potential on-target off-tumour events, are confined to the liver compartment with no involvement of other organs. Here we summarise the research steps to develop T cell therapy that utilises viral antigen as a tumour antigen in HBV-related HCC and discuss the efficacy and the potential mechanisms of action of HBV-specific T cell receptor (TCR)-redirected T cells in phase I clinical trials.

HBV慢性感染患者发生肝细胞癌的标志是通过一个高度组织特异性的过程表达全部或部分HBV抗原，这是由HBV的嗜肝性决定的。因此，HBV抗原是过继性T细胞免疫治疗的可能靶标，因为它们的表达和潜在的靶外肿瘤事件局限于肝室，不涉及其他器官。在这里，我们总结了利用病毒抗原作为肿瘤抗原在hbv相关HCC中开发T细胞疗法的研究步骤，并讨论了hbv特异性T细胞受体（TCR）重定向T细胞在I期临床试验中的疗效和潜在作用机制。

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 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.smim.2025.102003

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

Over the past decades, Interleukin-9 (IL-9) and T_H9 cells, have gained attention as important regulators of diverse responses throughout the promotion of activation and expansion of diverse cell subtypes. T_H9 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_H9 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_H9 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_H9-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.

在过去的几十年里，白细胞介素-9 （IL-9）和TH9细胞作为促进多种细胞亚型激活和扩增的多种反应的重要调节因子而受到关注。TH9细胞已在多种免疫学背景下被研究，包括过敏和自身免疫反应、癌症和传染病；这是最新的一种，特别是寄生虫引起的，是本文的重点。TH9细胞已成为针对寄生虫（包括蛔虫、扁虫、绦虫和钩虫）的免疫反应的关键介质；然而，截至2016年发表的研究中，受该细胞亚群影响的寄生虫病数量仍然有限。在本文中，我们旨在总结有关TH9细胞和IL-9在寄生虫感染中的作用的最新发现，以期对该领域的最新知识提供一个全面的概述，包括从未研究过的寄生虫模型。我们收集了最近的证据，强调IL-9的保护和致病作用，讨论了在寄生虫感染期间揭示TH9-IL-9介导反应的复杂性的挑战，以及治疗干预的机会，这将有助于将新发现转化为未来的临床应用。

{"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":"2025-11-01","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

Interleukin-1β and cancer immune response 白细胞介素-1β与癌症免疫反应

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-11-01 DOI: 10.1016/j.smim.2025.102002

Cédric Rébé, François Ghiringhelli

IL-1β belongs to the IL-1 family and has the particularity to need to be cleaved by caspase-1 to be active. Once processed, IL-1β is secreted and binds to IL-1R1 on target cells, leading to the transcription of specific genes. Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts or cancer cells and has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration and metastasis. Thus, depending on the cancer type, the treatments or the tumor microenvironment (TME), IL-1β has opposite effects on cancer progression, thus raising the question of inducing or inhibiting IL-1β. Here, we will analyze the impact of IL-1β on cancer cells and immune cells of the TME in different types of cancers.

IL-1β属于IL-1家族，具有需要被caspase-1切割才能激活的特殊性。一旦加工，IL-1β被分泌并与靶细胞上的IL-1R1结合，导致特定基因的转录。在肿瘤内，IL-1β由多种细胞类型（如免疫细胞、成纤维细胞或癌细胞）产生和分泌，对免疫细胞、血管生成、癌细胞增殖、迁移和转移具有多种作用。因此，根据癌症类型，治疗或肿瘤微环境（TME）， IL-1β对癌症进展具有相反的作用，从而提出了诱导或抑制IL-1β的问题。在这里，我们将分析IL-1β对不同类型癌症的癌细胞和TME免疫细胞的影响。

引用次数: 0

Antiviral humoral immunity: Enemy or ally of viral immunotherapy? 抗病毒体液免疫：病毒免疫治疗的敌人还是盟友？

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-10-24 DOI: 10.1016/j.smim.2025.102001

Maria Eugenia Davola, Olga Cormier, Karen Mossman

Oncolytic viruses are gaining traction as novel cancer immunotherapy tools given their ability to selectively target transformed cells. While direct tumor debulking was historically considered their primary mode of action, it is now appreciated that antitumor immunity significantly contributes to therapeutic efficacy. While T cells play a key role, less is known about humoral immunity in oncolytic virotherapy. While systemic delivery is the clinically preferred route for therapy administration, most oncolytic viruses are delivered directly to the tumor to avoid neutralization by pre-existing or therapy-induced immunity. In this review, we discuss emerging data showing the contribution of antiviral immunity to oncolytic activity along with growing evidence that questions dogma surrounding inhibitory activity of neutralizing antibodies. We further discuss how route of administration, tumor vascularization, host and cellular range, and oncolytic virus mechanism of action influence the role of the humoral immune response to therapy outcomes. We end the discussion with additional factors to consider, such as regulatory B cells, immunoglobulin isotype, Fc-mediated functions and the importance of choosing the right pre-clinical model that may contribute to overall therapy outcomes that are not routinely considered in pre-clinical and clinical studies of viral immunotherapies.

溶瘤病毒具有选择性靶向转化细胞的能力，因此作为新型癌症免疫治疗工具越来越受到关注。虽然直接肿瘤减体积历来被认为是它们的主要作用方式，但现在人们认识到抗肿瘤免疫显著有助于治疗效果。虽然T细胞发挥了关键作用，但对溶瘤病毒治疗中的体液免疫知之甚少。虽然全身给药是临床首选的治疗途径，但大多数溶瘤病毒是直接给药到肿瘤中，以避免被预先存在的或治疗诱导的免疫中和。在这篇综述中，我们讨论了显示抗病毒免疫对溶瘤活性的贡献的新数据，以及越来越多的证据，质疑围绕中和抗体抑制活性的教条。我们进一步讨论了给药途径、肿瘤血管化、宿主和细胞范围以及溶瘤病毒的作用机制如何影响体液免疫反应对治疗结果的作用。我们以其他需要考虑的因素结束讨论，如调节性B细胞、免疫球蛋白同型、fc介导的功能，以及选择正确的临床前模型的重要性，这些模型可能有助于整体治疗结果，而这些在病毒免疫治疗的临床前和临床研究中通常没有考虑到。

{"title":"Antiviral humoral immunity: Enemy or ally of viral immunotherapy?","authors":"Maria Eugenia Davola, Olga Cormier, Karen Mossman","doi":"10.1016/j.smim.2025.102001","DOIUrl":"10.1016/j.smim.2025.102001","url":null,"abstract":"<div><div>Oncolytic viruses are gaining traction as novel cancer immunotherapy tools given their ability to selectively target transformed cells. While direct tumor debulking was historically considered their primary mode of action, it is now appreciated that antitumor immunity significantly contributes to therapeutic efficacy. While T cells play a key role, less is known about humoral immunity in oncolytic virotherapy. While systemic delivery is the clinically preferred route for therapy administration, most oncolytic viruses are delivered directly to the tumor to avoid neutralization by pre-existing or therapy-induced immunity. In this review, we discuss emerging data showing the contribution of antiviral immunity to oncolytic activity along with growing evidence that questions dogma surrounding inhibitory activity of neutralizing antibodies. We further discuss how route of administration, tumor vascularization, host and cellular range, and oncolytic virus mechanism of action influence the role of the humoral immune response to therapy outcomes. We end the discussion with additional factors to consider, such as regulatory B cells, immunoglobulin isotype, Fc-mediated functions and the importance of choosing the right pre-clinical model that may contribute to overall therapy outcomes that are not routinely considered in pre-clinical and clinical studies of viral immunotherapies.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"80 ","pages":"Article 102001"},"PeriodicalIF":7.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362939","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

Three’s company: The cooperative signals behind the differentiation of Th9 cells 三人行：Th9细胞分化背后的合作信号。

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-10-16 DOI: 10.1016/j.smim.2025.101999

J. Alejandra Rodriguez, Humayra Habib, Matthew R. Olson

T helper 9 (Th9) cells, characterized by their production of interleukin-9 (IL-9), play pivotal roles in protective immunity and inflammatory disease. Their differentiation depends on the integration of three signals: TCR engagement (Signal 1), co-stimulatory receptor activation (Signal 2), and cytokine-driven transcriptional programming (Signal 3). This review explores how these signals converge to shape Th9 identity, highlighting the unique requirement for strong TCR signaling, heightened sensitivity to NF-κB signaling pathways, and the interplay of cytokine/STAT proteins. Understanding these mechanisms offers insights into Th9 biology and therapeutic strategies for cancer, allergy, and autoimmune disease.

T辅助性9 （Th9）细胞以产生白细胞介素-9 （IL-9）为特征，在保护性免疫和炎症性疾病中发挥关键作用。它们的分化取决于三个信号的整合：TCR参与（信号1）、共刺激受体激活（信号2）和细胞因子驱动的转录编程（信号3）。这篇综述探讨了这些信号如何汇聚形成Th9身份，强调了对强TCR信号的独特要求，对NF-κB信号通路的高度敏感性，以及细胞因子/STAT蛋白的相互作用。了解这些机制有助于深入了解Th9生物学以及癌症、过敏和自身免疫性疾病的治疗策略。

引用次数: 0

Unlocking IL-18: A hidden key in cancer immunity 解锁IL-18：癌症免疫的隐藏钥匙

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-10-06 DOI: 10.1016/j.smim.2025.101997

Shima Sepehri-Manesh , Marion Debeaud , Valerie Vouret-Craviari

The IL-1 family comprises 11 cytokines, including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-18, IL-33, and IL-36 cytokines to IL-37 and IL-38, that modulate innate immune system activity. In addition to their role in innate immunity, IL-1 family members can activate and enhance the function of polarized T cells. For example, IL-33 primarily influences T helper 2 (T_H2) cells, IL-1 plays a central role in the differentiation of T_H17 cells, and IL-18 predominantly affects T_H1 cells. The IL-1 family members participated in various biological functions as described elsewhere in this special issue. Here, we provide an overview on IL-18, originally called IFN-γ inducing factor, and its role in impacting cancer immunity.

IL-1家族包括11种细胞因子，包括IL-1α、IL-1β、IL-1受体拮抗剂（IL-1Ra）、IL-18、IL-33和IL-36到IL-37和IL-38，它们调节先天免疫系统的活性。除了在先天免疫中发挥作用外，IL-1家族成员还可以激活和增强极化T细胞的功能。例如，IL-33主要影响T辅助2 （TH2）细胞，IL-1在TH17细胞的分化中起核心作用，IL-18主要影响TH1细胞。IL-1家族成员参与了本特刊其他地方描述的各种生物学功能。在这里，我们概述了IL-18，最初被称为IFN-γ诱导因子，及其在影响癌症免疫中的作用。

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 Q1 IMMUNOLOGY

Seminars in Immunology

Pub 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

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 Reoviridae 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.

呼肠孤病毒是临床研究最多的溶瘤病毒之一，迄今已进行了50多项临床试验，治疗了1700多名患者。尽管呼肠孤病毒尚未获得完全的监管批准，但由于其在恶性细胞中的优先复制、在正常组织中的毒性最小、可通过多种途径传递以及强免疫刺激特性，它仍然是一种有希望的肿瘤免疫治疗溶瘤病毒候选物。呼肠孤病毒是呼肠孤病毒科的一种非包膜双链RNA病毒，与它的致病性亲戚轮状病毒不同，呼肠孤病毒在健康个体中通常是无症状的，因此对临床应用特别有吸引力。最近的研究已经大大扩展了其治疗潜力，超越了直接溶瘤，强调了其重塑肿瘤微环境、激活先天和适应性免疫、与化疗、放疗和免疫检查点抑制剂协同的能力。此外，口服给药、纳米颗粒包封、间充质干细胞介导转运和基因工程技术的进步，进一步提高了其安全性、靶向精确性和治疗效果。本综述总结了呼肠孤病毒为基础的病毒治疗的最新突破，并探讨了可能释放其作为下一代免疫治疗平台的全部潜力的新兴策略。

{"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":"2025-09-30","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

Latest insights into oncolytic viro-immunotherapy with vesicular stomatitis virus 囊性口炎病毒溶瘤病毒免疫治疗的最新进展。

IF 7.8 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-09-29 DOI: 10.1016/j.smim.2025.101996

Manuela Lizarralde-Guerrero , David Olagnier , Fernando Aranda , Maria Chiara Maiuri , Guido Kroemer , Jonathan G. Pol

Vesicular stomatitis virus (VSV), a rhabdovirus with intrinsic oncolytic properties, has emerged as a promising candidate for cancer therapy. Thanks to impaired antiviral responses affecting cancer cells, particularly downregulated type I interferon signaling, VSV selectively replicates in tumor cells while sparing normal cells. To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed. This review highlights the latest advances in VSV-based oncolytic virotherapy, focusing on novel modifications of the viral genome, as well as on combination strategies designed to enhance tumor selectivity, stimulate antitumor responses, and overcome resistance mechanisms. Recent studies have introduced modifications that bolster immunogenicity, and improve viral replication within tumors. Additionally, approaches combining VSV with small molecules, immune checkpoint inhibitors and other immunomodulatory agents, promise to augment antitumor activity. Emerging evidence suggests that VSV can reshape the tumor microenvironment, thus promoting robust adaptive antitumor immune responses. Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment.

水疱性口炎病毒（VSV）是一种具有固有溶瘤特性的横纹肌病毒，已成为一种有前途的癌症治疗候选病毒。由于影响癌细胞的抗病毒反应受损，特别是I型干扰素信号下调，VSV选择性地在肿瘤细胞中复制，同时保留正常细胞。为了减轻神经毒性和提高治疗效果，已经开发了VSV-∆M51、VSV- mifn β和VSV- gp等基因工程菌株。本文综述了基于vsv的溶瘤病毒治疗的最新进展，重点介绍了病毒基因组的新修饰，以及旨在提高肿瘤选择性、刺激抗肿瘤反应和克服耐药机制的联合策略。最近的研究引入了增强免疫原性的修饰，并改善了肿瘤内的病毒复制。此外，将VSV与小分子、免疫检查点抑制剂和其他免疫调节剂联合使用的方法有望增强抗肿瘤活性。新出现的证据表明VSV可以重塑肿瘤微环境，从而促进强大的适应性抗肿瘤免疫反应。正在进行的研究继续探索改善全身递送、最小化脱靶效应和增强病毒在肿瘤床内持久性的策略。进一步的研究和临床转化将确定基于vsv的病毒免疫疗法在癌症治疗中的全部潜力。

{"title":"Latest insights into oncolytic viro-immunotherapy with vesicular stomatitis virus","authors":"Manuela Lizarralde-Guerrero , David Olagnier , Fernando Aranda , Maria Chiara Maiuri , Guido Kroemer , Jonathan G. Pol","doi":"10.1016/j.smim.2025.101996","DOIUrl":"10.1016/j.smim.2025.101996","url":null,"abstract":"<div><div>Vesicular stomatitis virus (VSV), a rhabdovirus with intrinsic oncolytic properties, has emerged as a promising candidate for cancer therapy. Thanks to impaired antiviral responses affecting cancer cells, particularly downregulated type I interferon signaling, VSV selectively replicates in tumor cells while sparing normal cells. To mitigate neurotoxicity and improve therapeutic efficacy, genetically-engineered strains, such as VSV-∆M51, VSV-mIFNβ, and VSV-GP, have been developed. This review highlights the latest advances in VSV-based oncolytic virotherapy, focusing on novel modifications of the viral genome, as well as on combination strategies designed to enhance tumor selectivity, stimulate antitumor responses, and overcome resistance mechanisms. Recent studies have introduced modifications that bolster immunogenicity, and improve viral replication within tumors. Additionally, approaches combining VSV with small molecules, immune checkpoint inhibitors and other immunomodulatory agents, promise to augment antitumor activity. Emerging evidence suggests that VSV can reshape the tumor microenvironment, thus promoting robust adaptive antitumor immune responses. Ongoing research continues to explore strategies for improving systemic delivery, minimizing off-target effects, and enhancing viral persistence within the tumor bed. Further investigation and clinical translation will determine the full potential of VSV-based viroimmunotherapy in cancer treatment.</div></div>","PeriodicalId":49546,"journal":{"name":"Seminars in Immunology","volume":"80 ","pages":"Article 101996"},"PeriodicalIF":7.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145201926","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

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Seminars in Immunology

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀