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Inhibition of leukotriene-B4 signalling-mediated host response to tuberculosis is a potential mode of adjunctive host-directed therapy 抑制白三烯-B4 信号介导的宿主对结核病的反应是宿主定向辅助疗法的一种潜在模式
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-19 DOI: 10.1111/imm.13781
Ushashi Banerjee, Salik Miskat Borbora, Madhura Guha, Vikas Yadav, V. Sanjay, Amit Singh, Kithiganahalli Narayanaswamy Balaji, Nagasuma Chandra
{"title":"Inhibition of leukotriene-B4 signalling-mediated host response to tuberculosis is a potential mode of adjunctive host-directed therapy","authors":"Ushashi Banerjee,&nbsp;Salik Miskat Borbora,&nbsp;Madhura Guha,&nbsp;Vikas Yadav,&nbsp;V. Sanjay,&nbsp;Amit Singh,&nbsp;Kithiganahalli Narayanaswamy Balaji,&nbsp;Nagasuma Chandra","doi":"10.1111/imm.13781","DOIUrl":"10.1111/imm.13781","url":null,"abstract":"<p>Treatment of tuberculosis (TB) is faced with several challenges including the long treatment duration, drug toxicity and tissue pathology. Host-directed therapy provides promising avenues to find compounds for adjunctively assisting antimycobacterials in the TB treatment regimen, by promoting pathogen eradication or limiting tissue destruction. Eicosanoids are a class of lipid molecules that are potent mediators of inflammation and have been implicated in aspects of the host response against TB. Here, we have explored the blood transcriptome of pulmonary TB patients to understand the activity of leukotriene B4, a pro-inflammatory eicosanoid. Our study shows a significant upregulation in the leukotriene B4 signalling pathway in active TB patients, which is reversed with TB treatment. We have further utilized our in-house network analysis algorithm, ResponseNet, to identify potential downstream signal effectors of leukotriene B4 in TB patients including STAT1/2 and NADPH oxidase at a systemic as well as local level, followed by experimental validation of the same. Finally, we show the potential of inhibiting leukotriene B4 signalling as a mode of adjunctive host-directed therapy against TB. This study provides a new mode of TB treatment along with mechanistic insights which can be further explored in pre-clinical trials.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 3","pages":"392-407"},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170960","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}
引用次数: 0
Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells 人类巨细胞病毒(hCMV)特异性记忆 T 细胞的单细胞转录组和 T 细胞抗原受体分析揭示了 CD8+ - 和 CD4+ - 细胞毒性 T 细胞的效应因子和前效应因子。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-19 DOI: 10.1111/imm.13783
Raunak Kar, Somdeb Chattopadhyay, Anjali Sharma, Kirti Sharma, Shreya Sinha, Gopalakrishnan Aneeshkumar Arimbasseri, Veena S. Patil
{"title":"Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells","authors":"Raunak Kar,&nbsp;Somdeb Chattopadhyay,&nbsp;Anjali Sharma,&nbsp;Kirti Sharma,&nbsp;Shreya Sinha,&nbsp;Gopalakrishnan Aneeshkumar Arimbasseri,&nbsp;Veena S. Patil","doi":"10.1111/imm.13783","DOIUrl":"10.1111/imm.13783","url":null,"abstract":"<p>Latent human cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Although T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking. Here, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analysing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental and functional memory T cell subsets such as, long-term memory precursors and effectors, T helper-17, T regulatory cells (T<sub>REGs</sub>) and cytotoxic T lymphocytes (CTLs) of both CD4 and CD8 origin. The hCMV-specific T<sub>REGs</sub>, in addition to being enriched for molecules known for their suppressive functions, showed enrichment for the interferon response signature gene sets. The hCMV-specific CTLs were of two types, the pre-effector- and effector-like. The co-clustering of hCMV-specific CD4-CTLs and CD8-CTLs in both pre-effector as well as effector clusters suggest shared transcriptomic signatures between them. The huge TCR clonal expansion of cytotoxic clusters suggests a dominant role in the protective immune response to CMV. The study uncovers the heterogeneity in the hCMV-specific memory T cells revealing many functional subsets with potential implications in better understanding of hCMV-specific T cell immunity. The data presented can serve as a knowledge base for designing vaccines and therapeutics.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 3","pages":"420-439"},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158068","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}
引用次数: 0
TREM1/DAP12 based novel multiple chain CAR-T cells targeting DLL3 show robust anti-tumour efficacy for small cell lung cancer 基于 TREM1/DAP12 的靶向 DLL3 的新型多链 CAR-T 细胞对小细胞肺癌显示出强大的抗肿瘤疗效。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-12 DOI: 10.1111/imm.13776
Fengqi Nie, Yuli Chen, Yanming Hu, Peng Huang, Xuefei Shi, Jingsheng Cai, Mantang Qiu, Enxiu Wang, Kaihua Lu, Ming Sun
{"title":"TREM1/DAP12 based novel multiple chain CAR-T cells targeting DLL3 show robust anti-tumour efficacy for small cell lung cancer","authors":"Fengqi Nie,&nbsp;Yuli Chen,&nbsp;Yanming Hu,&nbsp;Peng Huang,&nbsp;Xuefei Shi,&nbsp;Jingsheng Cai,&nbsp;Mantang Qiu,&nbsp;Enxiu Wang,&nbsp;Kaihua Lu,&nbsp;Ming Sun","doi":"10.1111/imm.13776","DOIUrl":"10.1111/imm.13776","url":null,"abstract":"<p>Small cell lung cancer (SCLC), recognized as the most aggressive subtype of lung cancer, presents an extremely poor prognosis. Currently, patients with small cell lung cancer face a significant dearth of effective alternative treatment options once they experience recurrence and progression after first-line therapy. Despite the promising efficacy of immunotherapy, particularly immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and various other tumours, its impact on significantly enhancing the prognosis of SCLC patients remains elusive. DLL3 has emerged as a compelling target for targeted therapy in SCLC due to its high expression on the membranes of SCLC and other neuroendocrine carcinoma cells, with minimal to no expression in normal cells. Our previous work led to the development of a novel multiple chain chimeric antigen receptor (CAR) leveraging the TREM1 receptor and DAP12, which efficiently activated T cells and conferred potent cell cytotoxicity. In this study, we have developed a DLL3-TREM1/DAP12 CAR-T (DLL3-DT CAR-T) therapy, demonstrating comparable anti-tumour efficacy against SCLC cells in vitro. In murine xenograft and patient-derived xenograft models, DLL3-DT CAR-T cells exhibited a more robust tumour eradication efficiency than second-generation DLL3-BBZ CAR-T cells. Furthermore, we observed elevated memory phenotypes, induced durable responses, and activation under antigen-presenting cells in DLL3-DT CAR-T cells. Collectively, these findings suggest that DLL3-DT CAR-T cells may offer a novel and potentially effective therapeutic strategy for treating DLL3-expressing SCLC and other solid tumours.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 3","pages":"362-374"},"PeriodicalIF":6.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101553","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}
引用次数: 0
Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen 通过表达 APC 靶向抗原的 mRNA 疫苗预防和治疗人乳头瘤病毒相关癌症。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-12 DOI: 10.1111/imm.13777
Xiaoxuan Li, Huiyan Wang, Wujiang Lai, Jinrong Liao, Wenyu Mo, Keke Huang, Liqing He, Xiaomei Liang, Zhibin Yu, Jiang Xu, Xianwu Hua, Fujun Hou, Jun Ding, William Wei-Guo Jia, Kuan Zhang, Yifeng Wang
{"title":"Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen","authors":"Xiaoxuan Li,&nbsp;Huiyan Wang,&nbsp;Wujiang Lai,&nbsp;Jinrong Liao,&nbsp;Wenyu Mo,&nbsp;Keke Huang,&nbsp;Liqing He,&nbsp;Xiaomei Liang,&nbsp;Zhibin Yu,&nbsp;Jiang Xu,&nbsp;Xianwu Hua,&nbsp;Fujun Hou,&nbsp;Jun Ding,&nbsp;William Wei-Guo Jia,&nbsp;Kuan Zhang,&nbsp;Yifeng Wang","doi":"10.1111/imm.13777","DOIUrl":"10.1111/imm.13777","url":null,"abstract":"<p>Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7<sup>+</sup> tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8<sup>+</sup> T-cell immune response was induced, contributing to preventing and curing of E6 and E7<sup>+</sup> tumour. Antigen-specific CD8<sup>+</sup> T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 3","pages":"375-391"},"PeriodicalIF":6.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109955","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}
引用次数: 0
Cooperative induction of CXCL chemokines by inflammatory cytokines and oxidized phospholipids 炎症细胞因子和氧化磷脂对 CXCL 趋化因子的协同诱导。
IF 4.9 3区 医学
Immunology Pub Date : 2024-03-11 DOI: 10.1111/imm.13773
Alma Hodzic, Bernd Gesslbauer, Valery Bochkov, Olga V. Oskolkova
{"title":"Cooperative induction of CXCL chemokines by inflammatory cytokines and oxidized phospholipids","authors":"Alma Hodzic,&nbsp;Bernd Gesslbauer,&nbsp;Valery Bochkov,&nbsp;Olga V. Oskolkova","doi":"10.1111/imm.13773","DOIUrl":"10.1111/imm.13773","url":null,"abstract":"<p>Inflammation is initiated and driven by a mixture of mediators, which modify effects of each other. This study analysed in vitro pro-inflammatory activity of inflammatory cytokines (TNFα and IL-1β) in a combination with a lipid DAMP molecule, oxidized palmitoyl-arachidonoyl-phosphatidylcholine (OxPAPC). The study was performed on endothelial and monocytic cell lines. The cells were treated with different concentrations of TNFα or IL-1β, OxPAPC and their combinations, either in the presence or absence of drugs regulating inflammation. Pro-inflammatory effects of TNFα/IL-1β and OxPAPC were estimated by analysis of chemokines CXCL8, CXCL2 and CXCL3 by ELISA and RT-PCR. Toxicity was determined by analysis of metabolic activity. Statistical significance was estimated by ANOVA and Dunnett's test. OxPAPC was a much weaker chemokine inducer as compared to TNFα or IL-1β. However, OxPAPC and TNFα/IL-1β together induced effects that were significantly stronger than the arithmetical sum of individual effects. This cooperative action of OxPAPC and TNFα was reversed by inhibitors of p38 MAPK. We hypothesise that the boosting of TNFα and IL-1β effects by OxPAPC may be more pathologically important than the action of the lipid alone. Inhibitors of p38 MAPK may become a tool for analysis of pathological role of oxidized phospholipids.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"173 2","pages":"286-295"},"PeriodicalIF":4.9,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Omicron breakthrough infections after triple-dose inactivated COVID-19 vaccination: A comprehensive analysis of antibody and T-cell responses 接种三剂 COVID-19 灭活疫苗后的 Omicron 突破性感染:抗体和 T 细胞反应的综合分析。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-10 DOI: 10.1111/imm.13764
Tiandan Xiang, Xufeng Quan, Hang Jia, Hua Wang, Boyun Liang, Sumeng Li, Xiaoyan Wang, Huadong Li, Xuemei Feng, Lei Fan, Ling Xu, Tong Wang, Shue Xiong, Dongliang Yang, Jia Liu, Xin Zheng
{"title":"Omicron breakthrough infections after triple-dose inactivated COVID-19 vaccination: A comprehensive analysis of antibody and T-cell responses","authors":"Tiandan Xiang,&nbsp;Xufeng Quan,&nbsp;Hang Jia,&nbsp;Hua Wang,&nbsp;Boyun Liang,&nbsp;Sumeng Li,&nbsp;Xiaoyan Wang,&nbsp;Huadong Li,&nbsp;Xuemei Feng,&nbsp;Lei Fan,&nbsp;Ling Xu,&nbsp;Tong Wang,&nbsp;Shue Xiong,&nbsp;Dongliang Yang,&nbsp;Jia Liu,&nbsp;Xin Zheng","doi":"10.1111/imm.13764","DOIUrl":"10.1111/imm.13764","url":null,"abstract":"<p>This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4<sup>+</sup> and CD8<sup>+</sup>, remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8<sup>+</sup> T-cell response, and the intensity of the spike protein-specific T-cell response was roughly comparable between WT and Omicron BA.5.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 2","pages":"313-327"},"PeriodicalIF":6.4,"publicationDate":"2024-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Featured Cover 精选封面
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-07 DOI: 10.1111/imm.13778
{"title":"Featured Cover","authors":"","doi":"10.1111/imm.13778","DOIUrl":"https://doi.org/10.1111/imm.13778","url":null,"abstract":"<p>Cover illustration: The cover image is based on the Original Article Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota by Huan Xiao et al., https://doi.org/10.1111/imm.13750.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"171 4","pages":"i"},"PeriodicalIF":6.4,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140063824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Flavonoid extracted from Epimedium attenuate cGAS-STING-mediated diseases by targeting the formation of functional STING signalosome 从淫羊藿中提取的黄酮类化合物可通过靶向形成功能性 STING 信号体来减轻 cGAS-STING 介导的疾病。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-07 DOI: 10.1111/imm.13771
Yan Wang, Guang Xu, Jincai Wen, Xiaomei Zhao, Huanying Zhao, Guiji Lv, Yingjie Xu, Ye Xiu, Junjie Li, Simin Chen, Qing Yao, Yuanyuan Chen, Lina Ma, Xiaohe Xiao, Junling Cao, Zhaofang Bai
{"title":"Flavonoid extracted from Epimedium attenuate cGAS-STING-mediated diseases by targeting the formation of functional STING signalosome","authors":"Yan Wang,&nbsp;Guang Xu,&nbsp;Jincai Wen,&nbsp;Xiaomei Zhao,&nbsp;Huanying Zhao,&nbsp;Guiji Lv,&nbsp;Yingjie Xu,&nbsp;Ye Xiu,&nbsp;Junjie Li,&nbsp;Simin Chen,&nbsp;Qing Yao,&nbsp;Yuanyuan Chen,&nbsp;Lina Ma,&nbsp;Xiaohe Xiao,&nbsp;Junling Cao,&nbsp;Zhaofang Bai","doi":"10.1111/imm.13771","DOIUrl":"10.1111/imm.13771","url":null,"abstract":"<p>Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow-derived macrophages (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN-β, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 and TNF-α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (<i>Trex1</i>) deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS-STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS-STING signalling pathway.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 2","pages":"295-312"},"PeriodicalIF":6.4,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059275","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}
引用次数: 0
Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1 具有复制能力和复制缺陷的单纯疱疹病毒 1 的溶瘤活性比较。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-05 DOI: 10.1111/imm.13775
Georg Lindner, Annika Walter, Clara L. Magnus, Katharina Rosenhammer, Bohdan Holoborodko, Victoria Koch, Sarah Hirsch, Luis Grossmann, Suqi Li, David M. Knipe, Neal DeLuca, Beatrice Schuler-Thurner, Stefanie Gross, Barbara Schwertner, Martina Toelge, Anette Rohrhofer, Sabine Stöckl, Richard J. Bauer, Gertrud Knoll, Martin Ehrenschwender, Sebastian Haferkamp, Barbara Schmidt, Philipp Schuster
{"title":"Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1","authors":"Georg Lindner,&nbsp;Annika Walter,&nbsp;Clara L. Magnus,&nbsp;Katharina Rosenhammer,&nbsp;Bohdan Holoborodko,&nbsp;Victoria Koch,&nbsp;Sarah Hirsch,&nbsp;Luis Grossmann,&nbsp;Suqi Li,&nbsp;David M. Knipe,&nbsp;Neal DeLuca,&nbsp;Beatrice Schuler-Thurner,&nbsp;Stefanie Gross,&nbsp;Barbara Schwertner,&nbsp;Martina Toelge,&nbsp;Anette Rohrhofer,&nbsp;Sabine Stöckl,&nbsp;Richard J. Bauer,&nbsp;Gertrud Knoll,&nbsp;Martin Ehrenschwender,&nbsp;Sebastian Haferkamp,&nbsp;Barbara Schmidt,&nbsp;Philipp Schuster","doi":"10.1111/imm.13775","DOIUrl":"10.1111/imm.13775","url":null,"abstract":"<p>In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 <i>d</i>106S with replication-competent T-VEC. High infectious doses of HSV-1 <i>d</i>106S killed melanoma (<i>n</i> = 10), head-and-neck squamous cell carcinoma (<i>n</i> = 11), and chondrosarcoma cell lines (<i>n</i> = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time. HSV-1 <i>d</i>106S and, to a lesser extent T-VEC, triggered caspase-dependent early apoptosis as shown by pan-caspase inhibition and specific induction of caspases 3/7, 8, and 9. HSV-1 <i>d</i>106S induced a higher ratio of apoptosis-inducing infected cell protein (ICP) 0 to apoptosis-blocking ICP6 than T-VEC. T-VEC was oncolytic for an extended period of time as viral replication continued, which could be partially blocked by the antiviral drug aciclovir. High doses of T-VEC, but not HSV-1 <i>d</i>106S, increased interferon-β mRNA as part of the intrinsic immune response. When markers of immunogenic cell death were assessed, ATP was released more efficiently in the context of T-VEC than HSV-1 <i>d</i>106S infection, whereas HMGB1 was induced comparatively well. Overall, the early oncolytic effect on three different tumour entities was stronger with the non-replicative strain, while the replication-competent virus elicited a stronger innate immune response and more pronounced immunogenic cell death.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":"172 2","pages":"279-294"},"PeriodicalIF":6.4,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Methyl-supplemented nutrition delays the development of autoimmune disease in pristane-induced murine lupus 补充甲基营养可延缓普里斯坦诱导的小鼠狼疮中自身免疫疾病的发展。
IF 6.4 3区 医学
Immunology Pub Date : 2024-03-02 DOI: 10.1111/imm.13774
Silviya Bradyanova, Iliyan Manoylov, Gabriela Boneva, Lidiya Kechidzhieva, Andrey Tchorbanov, Kalina Nikolova-Ganeva
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