Clinical & Translational Immunology最新文献

{"title":"SIRT7 ameliorates Th17/Treg imbalance by desuccinylation of STAT3 to improve immune thrombocytopenia","authors":"Jiao Ge,&nbsp;Xiaoyan Zhang,&nbsp;Fajuan Tang,&nbsp;Yan Liu","doi":"10.1002/cti2.70048","DOIUrl":"https://doi.org/10.1002/cti2.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The imbalance of Th17/Treg cells represents a key pathogenic mechanism in immune thrombocytopenia (ITP); however, the underlying regulatory mechanisms remain poorly understood. Dysregulated succinylation has been implicated in disease onset and progression. Therefore, this study aimed to investigate the role of succinylation in modulating the Th17/Treg balance in ITP and to elucidate the associated molecular pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole blood samples were collected from ITP patients and mouse models. The frequencies of Treg and Th17 cells were quantified using flow cytometry. Treg- and Th17-associated biomarkers were analysed via enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction and immunoblotting. The regulatory relationship between SIRT7 and STAT3 succinylation was evaluated through co-immunoprecipitation, immunofluorescence and immunoblotting assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with ITP exhibited elevated Th17/Treg ratios, accompanied by increased global succinylation levels and reduced SIRT7 expression. Overexpression of SIRT7 restored the Th17/Treg imbalance <i>in vitro</i>. Mechanistically, SIRT7 overexpression suppressed STAT3 succinylation at K573, thereby inhibiting STAT3 activity and downstream signalling. Conversely, enforced STAT3 expression counteracted the effects of SIRT7 overexpression on Th17/Treg dynamics. <i>In vivo</i> experiments demonstrated that SIRT7 knockout exacerbated thrombocytopenia and further disrupted Th17/Treg homeostasis in murine models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SIRT7 mitigates ITP progression by maintaining Th17/Treg equilibrium through desuccinylation of STAT3. These findings highlight SIRT7 as a potential therapeutic target for ITP treatment, offering novel insights into the epigenetic regulation of immune dysregulation in autoimmune diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered iPSC-derived natural killer cells: recent innovations in translational innate anti-cancer immunotherapy","authors":"Jane Sun,&nbsp;Melissa Elliott,&nbsp;Fernando Souza-Fonseca-Guimaraes","doi":"10.1002/cti2.70045","DOIUrl":"https://doi.org/10.1002/cti2.70045","url":null,"abstract":"<p>Natural killer (NK) cells are increasingly recognised as potent tumoricidal agents that can be utilised for cancer immunotherapy. Their innate cytotoxicity against tumor cells, and reduced risk of causing transplantation or toxicity issues in patients, makes them a valuable option for exploration in allogeneic adoptive cell immunotherapies. However, sourcing NK cells from peripheral blood poses challenges in terms of scalability, consistency and variability. Induced pluripotent stem cells (iPSCs) are emerging as a platform to create specific cells with highly controlled processes, allowing for a common cell source for cell therapies and offering a promising inexhaustible source of genetically modifiable NK cells. This review highlights recent developments in the field of generating iPSC-derived NK cells in defined culture systems, and advancements in genetic modification to improve iPSC-NK cell therapy. We further discuss the development of iPSC banks and examine the potential of these cells in next-generation immunotherapies. Finally, we summarise the improvements in cancer targeting, expansion, persistence and cytotoxic functionality of iPSC-derived NK (iNK) cells both <i>in vitro</i> and <i>in vivo</i>, achieved through genetic modification of iPSCs, as well as recent related clinical trials.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data standards for single-cell RNA-sequencing of paediatric cancer","authors":"","doi":"10.1002/cti2.70044","DOIUrl":"https://doi.org/10.1002/cti2.70044","url":null,"abstract":"<p>Xiaohan Xu, John Saxon, Megan Sioe Fei Soon, Colin YC Lee &amp; Zewen Kelvin Tuong</p><p><b>Correction to:</b> Clin Transl Immunol 2025; 14: e70033. https://doi.org/10.1002/cti2.70033</p><p>There is an error within a sentence within the first paragraph of the ‘Lack of important annotations’ section, as follows:</p><p>Moreover, a striking 83% of data sets did not provide adequate clinical features of each patient sample (e.g. sex, age, disease stage and treatment history) (Figure <b>3d</b>).</p><p>This should have read:</p><p>Moreover, 17% of data sets did not provide adequate clinical features of each patient sample (e.g. sex, age, disease stage and treatment history) (Figure <b>3d</b>).</p><p>The authors apologise for this error.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of immunochemotherapy maintenance in metastatic nasopharyngeal carcinoma: insights from a cohort study in an endemic region","authors":"Zhuoying Luo,&nbsp;Yue Xia,&nbsp;Yuping Zhao,&nbsp;Haoyang Huang,&nbsp;Ying Deng,&nbsp;Zejiang Zhan,&nbsp;Yingying Huang,&nbsp;Xun Cao,&nbsp;Xi Chen,&nbsp;Jiayu Zhou,&nbsp;Chixiong Liang,&nbsp;Weixiong Xia,&nbsp;Liangru Ke,&nbsp;Xuehua Wei,&nbsp;Jinling Duan,&nbsp;Xing Lv,&nbsp;Hu Liang","doi":"10.1002/cti2.70043","DOIUrl":"https://doi.org/10.1002/cti2.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Metastatic nasopharyngeal carcinoma (mNPC) following palliative chemotherapy has high incidence and mortality rates. While maintenance therapy shows promising potential, the optimal strategy remains undefined. This study aimed to evaluate the therapeutic efficacy of immunochemotherapy maintenance in patients with mNPC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cohort study evaluated the therapeutic efficacy of combined maintenance therapy with capecitabine and anti-PD-1 antibodies in mNPC patients, using a prospectively maintained database. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival and safety profile. Furthermore, stratification analysis and sensitivity analysis were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 300 mNPC patients treated at Sun Yat-sen University Cancer Center from 2018 to 2023. Two hundred and thirty-four patients (78.0%) were male, and the median age was 45 years [interquartile range (IQR): 36–54]. At median follow-up of 43.6 months (IQR: 31.8–57.8), combination maintenance significantly improved PFS compared to single-drug maintenance [weighted hazard ratio (HR) 0.580, 95% confidence interval (95% CI) 0.387–0.872, <i>P</i> = 0.009; E-value, 2.27]. Stratification analysis revealed enhanced efficacy of immunochemotherapy maintenance in patients without prior local treatment (HR 0.414, 95% CI 0.224–0.767, <i>P</i> = 0.005) or with elevated premaintenance Epstein–Barr virus (EBV) DNA levels (HR 0.063, 95% CI 0.007–0.548, <i>P</i> = 0.012). No significant difference in PFS was observed between the capecitabine and anti-PD-1 single-agent groups. Notably, combination therapy yielded significantly longer PFS than either single-drug regimen. The safety profile was similar between combination maintenance and single-drug groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Combined maintenance therapy with anti-PD-1 antibodies and capecitabine may be a feasible treatment strategy for mNPC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular hierarchy for understanding heterogeneity of acute myeloid leukaemia with t(8;21)/RUNX1-RUNX1T1","authors":"Yibo Wu,&nbsp;Xiaolin Yuan,&nbsp;Xiaoyu Lai,&nbsp;Lizhen Liu,&nbsp;Yue Liang,&nbsp;Lihong Ni,&nbsp;Luxin Yang,&nbsp;Shanshan Hu,&nbsp;Jimin Shi,&nbsp;Jian Yu,&nbsp;Yanmin Zhao,&nbsp;Weiyan Zheng,&nbsp;Jie Sun,&nbsp;Yuanyuan Zhu,&nbsp;Wenjun Wu,&nbsp;Zhen Cai,&nbsp;He Huang,&nbsp;Shanshan Pei,&nbsp;Yi Luo","doi":"10.1002/cti2.70042","DOIUrl":"https://doi.org/10.1002/cti2.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Differentiation hierarchies in myeloid malignancies influence therapeutic response and prognosis. Acute myeloid leukaemia (AML) with t(8;21) is one of the most recurrent genetic subtypes of AML and is considered a distinct entity with shared characteristics. However, clinical outcomes remain markedly heterogeneous. This study aimed to investigate the relationship between leukaemic arrest at specific differentiation stages, genomic profiles and clinical outcomes in t(8;21) AML.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective study involving 338 patients with t(8;21) AML from three clinical centres in China. Patients received either chemotherapy alone (49.11%, <i>n</i> = 166) or chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT; 41.72%, <i>n</i> = 141). Immunophenotypic profiling classified patients into progenitor subgroups: MPP (20.12%, <i>n</i> = 68), lymphoid-primed multi-potent progenitor (14.50%, <i>n</i> = 49), CMP (12.72%, <i>n</i> = 43), GMP (24.85%, <i>n</i> = 84) and GP/MP (10.36%, <i>n</i> = 35). Based on differentiation stage, patients were categorised as primitive (Immuno-Prim; 47.34%, <i>n</i> = 160) or monocytic (Immuno-Mono; 35.21%, <i>n</i> = 119).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Immuno-Mono group was associated with lower 2-year overall survival (OS) and a higher 2-year cumulative incidence of relapse (CIR) compared to the Immuno-Prim group. Patients with a KIT mutation had poorer 2-year OS and higher 2-year CIR than those without the mutation. In the allo-HSCT cohort, the Immuno-Mono group continued to show lower 2-year OS and higher 2-year CIR relative to the Immuno-Prim group. Neither gene mutations (aside from KIT) nor chromosomal losses significantly affected OS or CIR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Leukaemic differentiation stage independently predicts post-treatment outcomes in t(8;21) AML. Arrest at specific myeloid stages correlates significantly with genetic aberrations, clinical presentation, therapeutic response and survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity","authors":"Kamila Bendíčková,&nbsp;Ioanna Papatheodorou,&nbsp;Gabriela Blažková,&nbsp;Martin Helán,&nbsp;Michaela Haláková,&nbsp;Petr Bednář,&nbsp;Erin Spearing,&nbsp;Lucie Obermannová,&nbsp;Julie Štíchová,&nbsp;Monika Dvořáková Heroldová,&nbsp;Tomáš Tomáš,&nbsp;Roman Panovský,&nbsp;Vladimír Šrámek,&nbsp;Marco De Zuani,&nbsp;Marcela Vlková,&nbsp;Daniel Růžek,&nbsp;Marcela Hortová-Kohoutková,&nbsp;Jan Frič","doi":"10.1002/cti2.70041","DOIUrl":"https://doi.org/10.1002/cti2.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Several years after the COVID-19 pandemic, the impact of SARS-CoV-2 on immunity and the potential protective role of Bacillus Calmette–Guérin (BCG) vaccination through trained immunity remain a subject of investigation. This study aimed to determine the long-term impact of SARS-CoV-2 on immune cells and the association between BCG vaccination, latent infections and COVID-19 severity and sepsis progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a prospective analysis of patients who recovered from mild/severe/critical COVID-19 (<i>n</i> = 97, 3–17 months after COVID-19) and sepsis patients (<i>n</i> = 64). First, we assessed the impact of COVID-19 and its severity on immune cell frequencies and expression of functional markers. Further, we analysed plasma titres of anti-<i>Toxoplasma gondii</i>/cytomegalovirus/BCG antibodies and their association with COVID-19 severity and sepsis outcome. To examine monocyte responses to secondary challenge, monocytes isolated from COVID-19 convalescent patients, BCG vaccinated and unvaccinated volunteers were stimulated with SARS-CoV-2 and LPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Post-COVID-19 patients showed immune dysregulation regardless of disease severity characterised by altered expression of activation and functional markers in myeloid (CD39, CD64, CD85d, CD11b) and lymphoid cells (CD39, CD57, TIGIT). Strikingly, post-critical COVID-19 patients showed elevated expression of CD57 in CD8⁺ T cells compared to other severity groups. A trend toward improved outcomes in BCG-seropositive COVID-19/sepsis patients was observed, although this may be confounded by age differences between groups. In contrast, the monocyte response to stimulation appeared unaffected by COVID-19 severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the long-term alterations of immune cells in post-COVID-19 patients, emphasising the substantial impact of COVID-19 on immune function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 7","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterisation of CD8+ T cells mobilised with acute supramaximal high-intensity interval exercise: implications for immune surveillance","authors":"Anna Strömberg,&nbsp;Mirko Mandić,&nbsp;Brennan J Wadsworth,&nbsp;Sebastian Proschinger,&nbsp;Seher Alam,&nbsp;Lisa MJ Eriksson,&nbsp;Laura Barbieri,&nbsp;Eric Rullman,&nbsp;Helene Rundqvist","doi":"10.1002/cti2.70037","DOIUrl":"https://doi.org/10.1002/cti2.70037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The beneficial influence of exercise on outcomes such as infection control and cancer prevention has been attributed partly to the immune system response during physical exertion. CD8⁺ T cells play a crucial role in immune surveillance, and in this study, we performed an in-depth analysis of the impact of supramaximal high-intensity exercise (HIIT) on CD8⁺ T-cell dynamics and function, which are currently lacking in the literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CD8⁺ T cells obtained from healthy human subjects before and after 3 × 30 s of HIIT were analysed <i>ex vivo</i> for viability and expansion properties, metabolic function using SeaHorse, IFN-gamma release using EliSpot, phenotype using RNA-seq and flow cytometry, and cytotoxic capacity by co-culture with HEK293T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Exercise led to a threefold increase in CD8⁺ T-cell count, and CD8⁺ T cells obtained after exercise had a more cytotoxic profile. Post-exercise CD8⁺ T cells had a lower glycolytic capacity than pre-exercise cells, and incubation of pre-exercise CD8⁺ T cells with post-exercise serum replicated this metabolic shift, suggesting a systemic effect of exercise on CD8⁺ T-cell metabolism. Importantly, CD8⁺ T cells maintained their viability and expansion properties despite the metabolic challenges induced by exercise. Functionally, post-exercise CD8⁺ T cells showed increased release of IFN-gamma and an enhanced unspecific cell killing capacity as demonstrated by co-culture with the immortalised cell line HEK293T.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The pronounced increase in the total number of circulating CD8⁺ T-cells with an increased cytotoxic capacity suggests a potential improvement in immune surveillance after acute HIIT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-lasting changes in circulating dendritic cell and monocyte subsets, and altered expression of EMR2, CD97 and EMR3 on these cells in the posttraumatic course","authors":"Leyu Zheng,&nbsp;Carolin Fuchs,&nbsp;Christian Kleber,&nbsp;Georg Osterhoff,&nbsp;Gabriela Aust","doi":"10.1002/cti2.70040","DOIUrl":"https://doi.org/10.1002/cti2.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Traumatic injury triggers the rapid release of damage-associated patterns (DAMPs). Dendritic cells (DCs) and monocytes play key roles in sensing, processing, and presenting DAMPs to naïve T cells. These heterogeneous immune cells express the adhesion GPCR EMR2/<i>ADGRE2</i>, which is likely regulated by DAMPs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the various blood DC and monocyte subsets in trauma patients and uninjured volunteers using flow cytometry. EMR2 and its closest relatives, CD97/<i>ADGRE5</i> and EMR3/<i>ADGRE3</i>, were quantified on these subsets to gain insights into their (patho)physiological regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following trauma, conventional and plasmocytoid DCs nearly disappeared from the circulation, which is inversely correlated with injury severity and adverse clinical parameters 120–240 h post injury. Alterations in EMR2 and CD97 on DCs were relatively minor. Classical monocytes increased, while non-classical monocytes showed a sustained decline in both absolute number and percentage, in a manner dependent on injury severity after trauma. EMR2 expression increased across all monocyte subsets, whereas CD97 showed little change. EMR3 expression decreased and remained low in classical monocytes, while it markedly increased in non-classical monocytes. These temporal patterns in adhesion GPRC expression were largely independent of injury severity and were observed in all injured patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Circulating DC and monocyte subsets underwent significant compositional changes after trauma, often correlating with injury severity and other clinical parameters. Despite structural similarities, EMR2, CD97, and EMR3 showed distinct regulatory patterns on monocyte subsets, suggesting different functional roles in the immune response to injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic ‘off-the-shelf’ SARS-CoV-2-specific adoptive T-cell therapy for refractory viral infection and end organ disease","authors":"Andrea S Henden,&nbsp;Katie E Lineburg,&nbsp;Archana Panikkar,&nbsp;Arushi Mahajan,&nbsp;Ricky Nelles,&nbsp;Emma Wright,&nbsp;Pauline Crooks,&nbsp;Jyothy Raju,&nbsp;Laetitia Le Texier,&nbsp;Srividhya Swaminathan,&nbsp;Leone Beagley,&nbsp;Shannon Best,&nbsp;Matthew Solomon,&nbsp;Hilary Reddiex,&nbsp;Glen Kennedy,&nbsp;Siok-Keen Tey,&nbsp;Michelle A Neller,&nbsp;Rajiv Khanna,&nbsp;Corey Smith","doi":"10.1002/cti2.70038","DOIUrl":"https://doi.org/10.1002/cti2.70038","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Despite the effective roll-out of COVID-19 vaccines, immunocompromised patients have a higher risk of morbidity and mortality following SARS-CoV-2 infection. Allogeneic adoptive T-cell immunotherapy is now established as an effective approach to treat viral diseases in immunocompromised patients. The objective of this study was to assess the safety of allogeneic virus-specific T-cell therapy in patients with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a repository of SARS-CoV-2-specific T cells generated from healthy exposed volunteers, we conducted an open-label phase I trial to assess the feasibility and safety of allogeneic SARS-CoV-2-specific T cells in immune-compromised cancer patients with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six participants at risk of severe COVID-19 were enrolled and received SARS-CoV-2-specific T-cell therapy within 4 days of recruitment. The first five participants who received two infusions of allogeneic SARS-CoV-2-specific T-cell therapy experienced no adverse events following treatment. Four of the six participants showed improvement in viral load following treatment and were alive at 12-week follow-up. One participant died 6 days after their second infusion, because of established pulmonary parenchymal damage following prolonged COVID infection. Another, who had underlying lupus nephritis, developed cytokine release syndrome and diffuse alveolar haemorrhage following a single infusion and was withdrawn from the study. They subsequently recovered from this serious adverse event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Allogeneic SARS-CoV-2-specific T-cell therapy provides a platform to rapidly administer T cells to high-risk COVID-19 patients. It was associated with a reduced viral load and increased SARS-CoV-2-specific T-cell responses in the majority of treated patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of CXCR5 expression and monocyte epithelial–mesenchymal transition are blood-borne signatures of sterile granulomatous diseases","authors":"Yuwei Hao,&nbsp;Anthea Anantharajah,&nbsp;Jane M Wells,&nbsp;Lyndell L Lim,&nbsp;Anthony JH Hall,&nbsp;Gary YJ Chew,&nbsp;Matthew C Cook","doi":"10.1002/cti2.70039","DOIUrl":"https://doi.org/10.1002/cti2.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Sarcoidosis is the exemplar sterile granulomatous disease and can affect any organ system. Tattoo uveitis (TU) resembles sarcoidosis clinically and histologically but is distinguished by the absence of systemic lymphadenopathy, with inflammation restricted to skin and eyes. In this study, our objectives were, first, to resolve whether TU is a subset of sarcoidosis or a different antigen-driven condition and, second, by comparing TU and sarcoidosis, to identify blood-borne signatures of active and quiescent sterile granulomatous diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited patients with active and inactive TU, sarcoidosis and healthy controls on whom we performed blood cell phenotyping and transcriptomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unlike sarcoidosis, active TU is characterised by marked CXCR5 down-regulation on B cells and CD4⁺ T cells that normalises on remission. TCR-VDJ sequencing reveals an antigen-driven response in sarcoidosis, but not in TU, with clonally expanded cytotoxic and terminally differentiated CD8⁺ effectors. Both active TU and sarcoidosis exhibit gene signatures of epithelial-to-mesenchymal transition (EMT) in circulating monocytes, whereas epithelioid macrophages are a hallmark of active granulomas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We have identified both shared and specific phenotypes in TU and sarcoidosis. Marked CXCR5 down-regulation occurs in active TU and could explain the unique absence of lymphadenopathy. Both TU and sarcoidosis are characterised by inflammatory monocyte phenotypes and transcriptional signatures of EMT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}