Clinical & Translational Immunology最新文献

{"title":"Lack of immunogenicity for an influenza-derived peptide across the HLA-B44 supertype molecules","authors":"Samuel Liwei Leong,&nbsp;Janesha C Maddumage,&nbsp;Stephanie Gras,&nbsp;Emma J Grant","doi":"10.1002/cti2.70051","DOIUrl":"https://doi.org/10.1002/cti2.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD8⁺ T cells are protective against influenza and there is an interest in designing a future CD8⁺ T-cell-mediated vaccine. However, a significant challenge is the extensive polymorphism of Human Leukocyte Antigen class I (HLA-I) molecules, the targets of CD8⁺ T cells. Despite this, HLA supertypes have been defined as a subset of HLA-I molecules sharing similar peptide motif preferences that may present overlapping peptide repertoires. Therefore, selecting immunogenic peptides presented by a range of HLA-I molecules for inclusion in a vaccine may partially overcome the challenge presented by HLA-I polymorphism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we investigated the presentation and immunogenicity of a known HLA-B*44:03-restricted influenza-derived peptide NS1_195-203 across the HLA-B44 supertype. Using TFold and AlphaFold2, we predicted the structures of the NS1_195-203 bound by the HLA-B44 supertype molecules, including HLA-B*44:02, HLA-B*44:03, HLA-B*40:01, HLA-B*40:01 and HLA-B*45:01. Peripheral blood mononuclear cells (PBMCs) isolated from donors expressing one of these HLA-B44 supertype molecules were used to generate CD8⁺ T-cell lines against the NS1_195-203 peptide and assess its immunogenicity via intracellular cytokine staining assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The structures predicted with TFold and AlphaFold2 of the NS1_195-203 peptide in complex with the HLA-B44 allomorphs were overall similar, with some notable differences at the peptide P9-Trp. A polyfunctional NS1_195-203-specific CD8⁺ T-cell response was observed in HLA-B*44:03⁺ and HLA-B*44:02⁺ samples; however, minimal responses were observed in the three other HLA-B44⁺ supertype molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although HLA molecules from the same supertype may be able to present the same peptide, this will not always result in CD8⁺ T-cell responses. As such, HLA-I supertypes, defined based on peptide binding motif and presentation, do not include information on immunogenicity and are not currently able to be used on their own to select epitopes as vaccine candidates. However, new knowledge on HLA supertypes may help curate sets of peptides that are potential vaccine targets and applicable to a range of HLA allomorphs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101845","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 effects of influenza and Bacille Calmette–Guérin vaccination on systemic inflammation","authors":"Priya A Debisarun,&nbsp;Rutger J Röring,&nbsp;Özlem Bulut,&nbsp;Thijs ten Doesschate,&nbsp;Thomas W van der Vaart,&nbsp;Vinod Kumar,&nbsp;Helga Lemmers,&nbsp;Heidi Dijkstra,&nbsp;Axel B Janssen,&nbsp;Karin Veerman,&nbsp;Rob ter Heine,&nbsp;Reinout van Crevel,&nbsp;Jaap ten Oever,&nbsp;Leo AB Joosten,&nbsp;Marc J Bonten,&nbsp;Cornelis H van Werkhoven,&nbsp;Janneke HHM van de Wijgert,&nbsp;Mihai G Netea","doi":"10.1002/cti2.70047","DOIUrl":"https://doi.org/10.1002/cti2.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Chronic systemic inflammation can lead to metabolic, cardiovascular and neurodegenerative complications, but the factors influencing it are incompletely understood. In this study, we evaluated several factors, including Bacille Calmette–Guérin (BCG) and influenza vaccination, SARS-CoV-2 infection and sex, that may impact systemic inflammation as assessed by targeted inflammatory plasma proteome analysis in healthy individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were randomised to BCG or placebo vaccination at the start of the Dutch SARS-CoV-2 epidemic in March/April 2020. They reported their influenza vaccination status for the most recent influenza season. Twelve weeks after BCG or placebo vaccination, we assessed relative concentrations of 69 proteins in plasma of 357 individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both BCG and quadrivalent influenza vaccination were associated with overall trends towards reduced systemic inflammation in both sexes, but with a more pronounced effect in men. However, the impact on specific immunological proteins varied between BCG and influenza vaccinations. SARS-CoV-2 infection in the 12 weeks between randomisation and plasma sampling was also associated with overall trends towards reduced systemic inflammation, reaching significance for CXCL10 and TNF concentrations. Notably, individuals who had received BCG vaccination prior to SARS-CoV-2 infection did not exhibit this protein profile. Furthermore, elevated CXCL11 and OPG concentrations at 12 weeks were associated with subsequent respiratory symptoms during the additional 9 months of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study revealed distinctive alterations in the plasma inflammation proteome associated with BCG vaccination, influenza vaccination, SARS-CoV-2 infection and sex. These findings are exploratory and hypothesis-generating and warrant further investigation in well-controlled longitudinal cohort studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 9","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037858","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":"Optimised modular anti-FLAG CAR T cells for solid tumor therapy","authors":"Xiaomeng Zhang,&nbsp;Rachel Xu,&nbsp;Dmitry Zorin,&nbsp;Evan G Pappas,&nbsp;Jiawei Tang,&nbsp;Yuchen Bai,&nbsp;Vicky M Qin,&nbsp;Bianca von Scheidt,&nbsp;Ruihong Huang,&nbsp;Weronika Kulakowska,&nbsp;Charbel Darido,&nbsp;Phillip K Darcy,&nbsp;Michael H Kershaw,&nbsp;Clare Y Slaney","doi":"10.1002/cti2.70046","DOIUrl":"https://doi.org/10.1002/cti2.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Chimeric antigen receptor (CAR) T cell therapies have transformed the treatment of B cell malignancies and show promise in other diseases, including autoimmune disorders and cardiac injury. However, broader application, particularly in solid tumours, is limited by challenges such as antigen escape and tumour heterogeneity. This study aimed to develop an anti-FLAG CAR capable of engaging FLAG-tagged secondary reagents, providing a flexible and adaptable targeting strategy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We engineered a humanised anti-FLAG CAR to engage FLAG-tagged secondary reagents. The initial construct exhibited tonic signalling, which was addressed through structural optimisation. Therapeutic efficacy was assessed in solid tumour mouse models expressing either FLAG or a FLAG-tagged secondary targeting reagent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The initial anti-FLAG CAR showed functional activity but exhibited tonic signalling and exhaustion, limiting its therapeutic utility. Structural optimisation significantly reduced exhaustion and improved T cell persistence and functionality. The optimised CAR T cells effectively inhibited tumour growth in models using either FLAG- engineered tumour cells or a FLAG-tagged secondary targeting reagent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings underscore the importance of CAR design in minimising exhaustion and enhancing therapeutic efficacy. This work supports a modular CAR T cell platform with the potential to overcome tumour antigen heterogeneity and immune evasion in solid cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885332","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":"Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia","authors":"Lewis J Williams,&nbsp;Connie SN Li-Wai-Suen,&nbsp;Alex L Garnham,&nbsp;Stefanie M Bader,&nbsp;Constantine S Tam,&nbsp;Ashley Whitechurch,&nbsp;Monica A Slavin,&nbsp;Marcel Doerflinger,&nbsp;Benjamin W Teh","doi":"10.1002/cti2.70049","DOIUrl":"https://doi.org/10.1002/cti2.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with relapsed and refractory CLL treated with ibrutinib were evaluated. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals (baseline, 3- and 6 months following commencement of ibrutinib) were analysed, with or without phorbol myristate acetate (PMA)/ionomycin stimulation, using Luminex and RNA sequencing. Luminex and gene expression profiles were compared between patients that who did and did not develop infection to identify immune signatures associated with infection over a subsequent 3-month period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-eight patients were included in this pilot study. Forty-six per cent of patients developed an infection (13 patients, 17 events) over 9 months of patient monitoring. Most infections were clinically diagnosed (72.7%) with the remainder microbiologically diagnosed bacterial (18.1%) and viral (9.2%) infections. Cell populations did not correlate with subsequent infection. An inflammatory transcriptome profile at 3 months following ibrutinib was associated with a subsequent infection episode. Increased whole protein response to PMA stimulation at 3 and 6 months was associated with subsequent risk for infections. Increased whole protein response to PMA stimulation was associated with subsequent risk of infection 3 months after commencing ibrutinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The combination of protein and RNA analysis can provide further insight into the interactions of immunotherapies and immunity but should be validated further in large cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 8","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767270","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":"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}