Immunology最新文献

{"title":"Use of a Foamy-Virus Vector System to Produce an 'Off-the-Shelf' Fcγ-CR-T Cell Product for the Treatment of Haematological and Solid Tumour Malignancies.","authors":"Ioanna Lazana, Emmanouil Simantirakis, Evangelos Kourous, Maria Daniil, Dimitris Ioannou, George Vassilopoulos","doi":"10.1111/imm.70018","DOIUrl":"https://doi.org/10.1111/imm.70018","url":null,"abstract":"<p><p>The emergence of chimeric antigen receptor (CAR)-T cells has revolutionised the therapeutic landscape of hematologic malignancies, with limited translation only to solid organ malignancies. Furthermore, safety concerns have recently been raised, in terms of tumorigenesis, relating to the viral vector systems used for gene transduction, underlying the need for alternative, safer gene therapy delivery systems. In this study, we investigated the use of foamy virus (FV) vectors, known for their favourable integration profile and reduced genotoxicity, to generate Fcγ (CD16)-chimeric receptor (CR) T cells. Our aim was to provide T cells with the capacity to recognise and bind to tumour cells, opsonised with commercially available monoclonal antibodies (mAbs), enhancing the antibody-dependent cell cytotoxicity (ADCC). The high-affinity F158V polymorphism of the CD16, previously shown to mediate superior ADCC, was utilised for the generation of Fcγ (CD16)-CR T cells. Results showed that FV-derived CD16-CR T cells exhibited robust CD16 expression and demonstrated potent functional activity, including: (i) high mAb-binding capacity, (ii) formation of T-cell tumour cell aggregates in the presence of mAbs, (iii) significant degranulation and proinflammatory cytokine production upon tumour engagement and (iv) potent, dose-dependent cytotoxic activity against target cells in the presence of mAbs. This is the first study, to our knowledge, demonstrating that FV vectors can be used to generate potent CD16-CR T cells, providing a safer and more versatile platform for antibody-based immunotherapy. This approach enables the expansion of engineered T cell therapies beyond hematologic malignancies and towards solid tumours, using clinically approved mAbs.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GD2-CAR T Cell Therapy for H3K27M⁺ Diffuse Intrinsic Pontine Glioma: A Phase I Clinical Trial and Mechanistic Insights.","authors":"Congfa Jiang, Hening Xu, Jianqiao Shentu, Shiwei Duan","doi":"10.1111/imm.70019","DOIUrl":"https://doi.org/10.1111/imm.70019","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC I of the Great Reed Warbler Promotes a Flat Peptide Binding Mode.","authors":"Raminta Venskutonytė, Sven Kjellström, Emily Amelia O'Connor, Helena Westerdahl, Karin Lindkvist-Petersson","doi":"10.1111/imm.70015","DOIUrl":"https://doi.org/10.1111/imm.70015","url":null,"abstract":"<p><p>The major histocompatibility complex (MHC) plays a key role in pathogen recognition as part of the adaptive immune system. MHC I gene copy numbers in birds of the order Passeriformes (songbirds) are substantially larger compared to other birds. MHC I diversity and antigen presentation have been carefully characterised in chicken Gallus gallus of the order Galliformes; chickens express few MHC I genes and often present antigens that bulge out of the peptide binding cleft. This observation raises the question of whether MHC I presents antigens in a similar way in species with many MHC genes? Here, we present the X-ray structure of MHC I from the great reed warbler Acrocephalus arundinaceus (Acar3) a long-distance migratory songbird. Structural analysis shows that MHC I binds the antigen in a flat conformation due to a sequentially well-conserved restriction point, acting like a pair of tweezers, within the peptide binding grove, created by Arg97 and Arg155. This more stringent antigen presentation by Acar MHC I molecules may partly explain the high MHC gene copy numbers seen in the great reed warbler.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Atorvastatin Promotes the Expansion of Myeloid-Derived Suppressor Cells and Attenuates Murine Colitis\".","authors":"","doi":"10.1111/imm.70009","DOIUrl":"https://doi.org/10.1111/imm.70009","url":null,"abstract":"","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascaris Lumbricoides Cystatin Impairs IL-1β Maturation and CD14 Expression in Human Monocytes.","authors":"Ana Lozano, Josefina Zakzuk, Nathalie Acevedo, Andrew R Williams, Luis Caraballo","doi":"10.1111/imm.70016","DOIUrl":"https://doi.org/10.1111/imm.70016","url":null,"abstract":"<p><p>Ascaris lumbricoides cystatin (Al-CPI), a cysteine protease inhibitor, has shown anti-inflammatory effects in models of house dust mite-induced respiratory allergy and experimental colitis. Since monocytes are primary targets of cystatins, and helminth-derived products can induce immunoregulatory monocytes that mitigate autoimmune and inflammatory diseases in murine models, we aimed to investigate the immunoregulatory effects of Al-CPI on human monocytes and its mechanisms. Monocytes were isolated from healthy donors using CD14+ magnetic beads and treated with recombinant Al-CPI (rAl-CPI) before activation with LPS. Surface marker expression and caspase-1 activity were analysed by flow cytometry, while cytokine levels were quantified using bead-based assays. Caspase-8 inhibition was measured by fluorescence, and pro-IL-1β expression was evaluated by Western blot. RNA-seq and differential gene expression analyses were performed using DESeq2 and GSEA. rAl-CPI reduced cell surface expression of HLA-DR and CD14 as well as IL-1β levels in cell culture supernatants. Transcriptomic analysis identified 30 differentially expressed genes (12 upregulated and 18 downregulated; padj < 0.05 and fold change [FC] < |1.5|), including the downregulation of CD14 and SLAMF1, both involved in LPS-mediated signalling through the TLR4-TRIF pathway. GSEA analysis showed that rAl-CPI plus LPS induced an enrichment of the IFN signalling pathway compared with LPS (NES = 1.88; padj < 0.0001). Further analysis of IL-1β production and maturation showed that rAl-CPI did not alter pro-IL-1β levels, but reduced caspase-1 activation. In conclusion, rAl-CPI may impair IL-1β maturation and release by modulating the alternative inflammasome activation, potentially through downregulation of CD14 and other key regulatory molecules involved in this pathway.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Mechanism of Anti-ICOS mAb in Experimental Autoimmune Encephalomyelitis.","authors":"Minjun Xiao, Yun Zhao, Xue Zhang, Qi Sun, Ge Gao, Nan Wu, Xueli Fan","doi":"10.1111/imm.70014","DOIUrl":"https://doi.org/10.1111/imm.70014","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Targeting costimulatory signalling pathways, especially inducible T-cell costimulatory (ICOS)-ICOS ligand(ICOSL) co-stimulatory signal, has been widely used as a therapeutic target in autoimmune diseases. Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disease in the central nervous system. At present, few studies are addressing the role of the ICOS-ICOSL co-stimulatory pathway in MS. We aimed to explore the role of anti-ICOS mAb in the immune response of EAE and further reveal the regulatory mechanism. C57BL/6 female mice (6-8 weeks old, 18-20 g) were randomly divided into EAE group, T1 group, T9 group and T30 group. The EAE model was established in the three groups by MOG active immunisation. Symptom scores and weights of mice were recorded every day after modelling. Mice in the T1 and the T9 groups were given intraperitoneal injections of anti-ICOS mAb on Day 1 or 9 after active immunisation, respectively. Anti-ICOS mAb were injected three times total, each injection separated by 72 h. On the 19th day after modelling, the mice were sacrificed and the spinal cord tissues of each group were collected. Mice in the T30 group were given an intraperitoneal injection of anti-ICOS mAb on Day 9 after active immunisation. These anti-ICOS mAb were injected continuously until Day 30. On Day 30 after the establishment of the model, the mice were sacrificed and spinal cord tissues were collected. HE staining was used to observe the inflammatory infiltration of the spinal cord in each group of mice. Transcriptome sequencing was used to detect gene transcription in spinal cord tissues of mice and to explore the signalling pathways that might be involved. Finally, the signalling pathway was verified by Western blot. (1) Compared with the EAE group, there are significantly lower behavioural scores, heavier weight, delayed onset time and fewer inflammatory infiltrations of the spinal cord in the T9 group and T30 group. However, there were no significant differences in behavioural scores, weight, onset time and inflammatory infiltration between the EAE group and the T1 group. (2) The R&lt;sup&gt;2&lt;/sup&gt; value of the spinal cord sample in each group was greater than 0.8. There were 6569 differentially expressed genes (DEGs) between T9 group and EAE group, including 2579 up-regulated genes and 3990 down-regulated genes. There were 487 DEGs between T1 and EAE groups, including 131 up-regulated genes and 356 down-regulated genes. There were 7116 DEGs between T9 and T1 groups, including 2921 up-regulated genes and 4195 down-regulated genes. KEGG enrichment showed that DEGs between T9 group and EAE group were mainly enriched in Epstein-Barr virus infection, NF-κB signalling pathway, FcγR-mediated phagocytosis, natural killer cell-mediated cytotoxicity, as well as Th17, Th1 and Th2 cell differentiation pathways. In the most significantly enriched EB pathway, we found that the fold change of key genes SYK, PI3K and AKT was -4.345","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct T Cell Receptor Clonotypes in the Sardinian Population Highlight the Role of Mucosal-Associated Invariant T Cells and Invariant Natural Killer T Cells in Multiple Sclerosis.","authors":"Jiaxin Shen, Elena Rita Simula, Yisu Liu, Gustavo Sganzerla Martinez, Xiaofen Wen, David J Kelvin, Leonardo A Sechi","doi":"10.1111/imm.70013","DOIUrl":"https://doi.org/10.1111/imm.70013","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, driven by T-cell mediated immune responses. Studying T-cell receptor (TCR) clonotypes specific to MS in distinct populations can provide insights into disease mechanisms. The Sardinian population, with its unique genetic background resulting from geographical isolation, presents a high-risk cohort for MS research, offering a valuable context for understanding the disease's pathogenesis. We analysed the frequency of unique TCR clonotypes in peripheral blood samples from Sardinian MS patients and healthy controls, focusing on TCRα and TCRβ CDR3 sequences. Clonotypes were functionally annotated for antigen-specific interactions, and hierarchical analysis was performed to identify shared TCR clonotypes between MS patients and healthy controls. A total of 119 TCRβ and 521 TCRα CDR3 clonotypes were significantly more frequent in MS patients compared to healthy controls (p < 0.05). Several TCR-α clonotypes, such as CAVLDSNYQLIW (a MAIT cell clonotype targeting the BST2 antigen) and CAVNTGNQFYF (cross-reactive to multiple antigens, including CMV p65 and BST2), were identified as specific to MS. Shared clonotype analysis revealed the involvement of mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells in MS pathogenesis. Notably, HCV-specific TCR-α clonotypes (NS3-HCV) were significantly increased in MS patients, suggesting a link between infectious disease-related and autoimmune-related clonotypes. No significant differences were observed for other antigens, such as VP22, p65 and BST2. This study identifies distinct TCR clonotypes associated with MS in the Sardinian population, highlighting the role of MAIT and iNKT cells in the disease's pathogenesis. The findings suggest that HCV-specific TCR repertoires may contribute to the development of MS. These results improve our understanding of T-cell mediated immune mechanisms in MS and offer potential targets for therapeutic intervention, particularly within the Sardinian cohort.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD73 Expression by CD4⁺ T Cells Marks Early Effector Memory T Cells.","authors":"Luxia Chen, Sabine Ring, Anna Jurga, Florian C Kurschus, Alexander Enk, Karsten Mahnke","doi":"10.1111/imm.70011","DOIUrl":"https://doi.org/10.1111/imm.70011","url":null,"abstract":"<p><p>CD73 is a membrane bound ectoenzyme, dephosphorylating adenosine mono- and di-phosphate to immunosuppressive adenosine. It is strongly expressed by CD4⁺CD25⁺Foxp3⁺ regulatory T cells, but when analysing conventional CD4⁺ T cells only 50% express CD73. When analysing these two clearly distinct (i.e., CD73⁺ and CD73^-) populations, we found that the naïve CD73⁺CD4⁺ subset exerted superior proliferation over the CD73^-CD4⁺ cells, was more resistant to activation induced cells death (AICD) and was prone to develop into a \"Th1-like\" cell type, expressing the prototypic cytokines (IFN-γ, TNF-α) and specific transcription factors (i.e., Tbx21). Upon transfer into lymphopenic hosts, CD73⁺CD4⁺ cells exhibited increased proliferation and survival, and accumulated in inflammatory tissues, developing a CD44⁺CD62L^- effector memory phenotype. Therefore, we conclude that CD73 in naïve CD4⁺ T cells functions as a promotor of survival and proliferation of T cells, as well as a marker for their further differentiation into effector T cells.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiofrequency Ablation and Immunotherapy: Orchestrating the Immune Microenvironment for Improved Hepatocellular Carcinoma Control.","authors":"Liu Yang, Shuhang Wei, Zongxin Liu, Qiqi Liu, Zhen Yu, Yuemin Feng, Qiang Zhu","doi":"10.1111/imm.70004","DOIUrl":"https://doi.org/10.1111/imm.70004","url":null,"abstract":"<p><p>Radiofrequency ablation (RFA) is a radical treatment modality for early-stage hepatocellular carcinoma (HCC). In addition to directly eliminating tumour cells, RFA induces changes in infiltrating cells within the liver tumour immune microenvironment (TIME), thereby eliciting anti-tumour immune effects. Moreover, incomplete radiofrequency ablation (IRFA) induces an immunosuppressive tumour microenvironment, which inhibits anti-tumour immune responses and promotes tumour recurrence and metastasis. Immunotherapy, a systemic treatment, activates or enhances the immune system to recognise and eliminate tumour cells. Thus, orchestrating the TIME makes it possible to combine RFA and immunotherapy, which may significantly enhance the anti-tumour immune response to target residual tumour cells. This combinatorial approach may emerge as a pivotal strategy to augment HCC control and mitigate post-RFA recurrence. This review discusses how RFA modulates the TIME in HCC, and the immune-related mechanisms leading to tumour cell survival and invasion after IRFA. Finally, we summarise the combined mechanisms of the two modalities on TIME, and their clinical implications for treating HCC, aiming to provide new insights for the combined strategy of RFA and immunotherapy.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γδT Cells in IBD: Beneficial or Detrimental?","authors":"Baoqing Xu, Jianbin Ji, Lingling Ma, Chunyan Wang, Lianjing Pang, QingChao Song, Yang Liu, Zhenghua Zhou, Fanfan Qu","doi":"10.1111/imm.70012","DOIUrl":"https://doi.org/10.1111/imm.70012","url":null,"abstract":"<p><p>γδT cells play a crucial role in inflammatory bowel disease (IBD). Studies have shown that the number, subsets and secreted cytokines of γδT cells undergo changes in IBD. However, whether γδT cells are beneficial or detrimental in IBD remains controversial. Some studies suggest that γδT cells have a protective role in colitis, while others indicate that the expansion and activation of γδT cells may exacerbate colitis. Several studies have explored γδT cell-based therapies for immune disorders, and γδT cell-based therapy for IBD has emerged as a promising research direction. There are numerous reviews of γδT cells and autoimmune diseases, but few reviews focus on γδT and IBD. Therefore, this article briefly summarises the current understanding of γδT cells in IBD.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}