Clinical & Translational Immunology最新文献_第4页

Lack of immunogenicity for an influenza-derived peptide across the HLA-B44 supertype molecules 流感衍生肽在HLA-B44超型分子中缺乏免疫原性

IF 3.8 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-09-19 DOI: 10.1002/cti2.70051

Samuel Liwei Leong, Janesha C Maddumage, Stephanie Gras, Emma J Grant

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

CD8+ T细胞对流感具有保护作用，未来设计一种CD8+ T细胞介导的疫苗很有兴趣。然而，一个重大的挑战是人类白细胞抗原I类（HLA-I）分子的广泛多态性，CD8+ T细胞的靶标。尽管如此，HLA超型被定义为HLA- 1分子的一个子集，它们具有相似的肽基序偏好，可能呈现重叠的肽谱。因此，选择一系列hla - 1分子呈现的免疫原性肽纳入疫苗可能部分克服hla - 1多态性带来的挑战。方法在本研究中，我们研究了一种已知的HLA-B*44:03限制性流感衍生肽NS1195-203在HLA-B44超型中的表达和免疫原性。利用TFold和AlphaFold2预测了HLA-B44超型分子结合的NS1195-203的结构，包括HLA-B*44:02、HLA-B*44:03、HLA-B*40:01、HLA-B*40:01和HLA-B*45:01。从供体中分离出表达其中一种HLA-B44超型分子的外周血单个核细胞（PBMCs）用于生成针对NS1195-203肽的CD8+ t细胞系，并通过细胞内细胞因子染色法评估其免疫原性。结果NS1195-203多肽与HLA-B44异型复合物的TFold和AlphaFold2预测结构总体相似，但P9-Trp多肽预测结构存在显著差异。在HLA-B*44:03+和HLA-B*44:02+样品中观察到多功能ns1195 -203特异性CD8+ t细胞应答；然而，在其他三种HLA-B44+超型分子中观察到最小的反应。结论：尽管来自相同超型的HLA分子可能呈现相同的肽，但这并不总是导致CD8+ t细胞反应。因此，基于肽结合基序和呈递定义的hla - 1超型不包括免疫原性信息，目前还不能单独用于选择作为候选疫苗的抗原表位。然而，关于HLA超型的新知识可能有助于筛选一组肽，这些肽是潜在的疫苗靶点，适用于一系列HLA异型。

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引用次数: 0

Long-term effects of influenza and Bacille Calmette–Guérin vaccination on systemic inflammation 流感和卡介苗接种对全身炎症的长期影响

IF 3.8 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-09-11 DOI: 10.1002/cti2.70047

Priya A Debisarun, Rutger J Röring, Özlem Bulut, Thijs ten Doesschate, Thomas W van der Vaart, Vinod Kumar, Helga Lemmers, Heidi Dijkstra, Axel B Janssen, Karin Veerman, Rob ter Heine, Reinout van Crevel, Jaap ten Oever, Leo AB Joosten, Marc J Bonten, Cornelis H van Werkhoven, Janneke HHM van de Wijgert, Mihai G Netea

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

目的慢性全身性炎症可导致代谢、心血管和神经退行性并发症，但其影响因素尚不完全清楚。在这项研究中，我们评估了几个因素，包括卡介苗和流感疫苗接种、SARS-CoV-2感染和性别，这些因素可能会影响健康个体的全身炎症，并通过靶向炎症血浆蛋白质组分析进行评估。方法在2020年3月/ 4月荷兰SARS-CoV-2流行开始时，参与者随机接种卡介苗或安慰剂。他们报告了最近流感季节的流感疫苗接种情况。接种卡介苗或安慰剂12周后，我们评估了357人血浆中69种蛋白质的相对浓度。结果卡介苗和四价流感疫苗接种在两性中都与减少全身性炎症的总体趋势相关，但在男性中效果更明显。然而，卡介苗和流感疫苗对特异性免疫蛋白的影响不同。在随机化和血浆取样之间的12周内，SARS-CoV-2感染也与全身炎症减少的总体趋势相关，对CXCL10和TNF浓度具有重要意义。值得注意的是，在感染SARS-CoV-2之前接种过卡介苗的个体没有表现出这种蛋白质谱。此外，12周时CXCL11和OPG浓度升高与随后9个月随访期间的呼吸道症状相关。结论：我们的研究揭示了血浆炎症蛋白组与卡介苗接种、流感疫苗接种、SARS-CoV-2感染和性别相关的显著变化。这些发现是探索性的和假设生成的，值得在控制良好的纵向队列研究中进一步调查。

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引用次数: 0

Optimised modular anti-FLAG CAR T cells for solid tumor therapy 优化模块化抗flag CAR - T细胞用于实体瘤治疗

IF 3.8 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-08-21 DOI: 10.1002/cti2.70046

Xiaomeng Zhang, Rachel Xu, Dmitry Zorin, Evan G Pappas, Jiawei Tang, Yuchen Bai, Vicky M Qin, Bianca von Scheidt, Ruihong Huang, Weronika Kulakowska, Charbel Darido, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

嵌合抗原受体（CAR） T细胞疗法已经改变了B细胞恶性肿瘤的治疗方法，并在包括自身免疫性疾病和心脏损伤在内的其他疾病中显示出希望。然而，广泛的应用，特别是在实体肿瘤中，受到诸如抗原逃逸和肿瘤异质性等挑战的限制。本研究旨在开发一种能够参与flag标记的二级试剂的抗flag CAR，提供灵活和适应性强的靶向策略。我们设计了一种人源化的抗flag CAR，利用flag标记的二级试剂。最初的结构表现出张力信号，这是通过结构优化来解决的。在表达FLAG或FLAG标记的二次靶向试剂的实体瘤小鼠模型中评估治疗效果。结果初始抗flag CAR具有功能活性，但表现为强直信号和耗竭，限制了其治疗作用。结构优化显著减少了耗竭，提高了T细胞的持久性和功能性。在使用FLAG工程肿瘤细胞或FLAG标记的二次靶向试剂的模型中，优化的CAR - T细胞有效地抑制肿瘤生长。结论：我们的研究结果强调了CAR设计在减少衰竭和提高治疗效果方面的重要性。这项工作支持模块化CAR - T细胞平台，具有克服实体癌肿瘤抗原异质性和免疫逃避的潜力。

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引用次数: 0

Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia 在高风险人群中阐明预测感染的新免疫特征：一项针对复发和难治性慢性淋巴细胞白血病患者的初步研究

IF 3.8 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-08-03 DOI: 10.1002/cti2.70049

Lewis J Williams, Connie SN Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, Benjamin W Teh

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

慢性淋巴细胞白血病（CLL）患者感染风险增加，复发和难治性患者感染风险更高。在布鲁顿酪氨酸激酶抑制剂等免疫疗法的时代，感染风险的临床评估越来越具有挑战性。进行了一项初步研究，以阐明可能的预测性免疫标志物。方法对伊鲁替尼治疗复发、难治性CLL患者进行评价。使用Luminex和RNA测序，在规定的时间间隔（基线，伊鲁替尼开始后3个月和6个月）收集外周血单个核细胞（PBMCs），在有或没有肉豆酸盐佛博尔酯(PMA)/离子霉素刺激下进行分析。比较发生感染和未发生感染的患者之间的Luminex和基因表达谱，以确定随后3个月期间与感染相关的免疫特征。结果28例患者纳入本初步研究。在9个月的患者监测中，46%的患者发生感染（13例患者，17例事件）。大多数感染是临床诊断的（72.7%），其余是微生物诊断的细菌（18.1%）和病毒（9.2%）感染。细胞数量与随后的感染无关。依鲁替尼后3个月的炎症转录组谱与随后的感染发作有关。在3个月和6个月时，全蛋白对PMA刺激的反应增加与随后的感染风险相关。对PMA刺激的全蛋白反应增加与开始使用伊鲁替尼3个月后的感染风险相关。结论结合蛋白和RNA分析可以进一步了解免疫治疗和免疫的相互作用，但还需要在更大的队列中进一步验证。

{"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, Connie SN Li-Wai-Suen, Alex L Garnham, Stefanie M Bader, Constantine S Tam, Ashley Whitechurch, Monica A Slavin, Marcel Doerflinger, 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}

引用次数: 0

SIRT7 ameliorates Th17/Treg imbalance by desuccinylation of STAT3 to improve immune thrombocytopenia SIRT7通过STAT3去乙酰化改善Th17/Treg失衡，从而改善免疫性血小板减少症

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-07-15 DOI: 10.1002/cti2.70048

Jiao Ge, Xiaoyan Zhang, Fajuan Tang, Yan Liu

Objectives

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.

Methods

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.

Results

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 in vitro. 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. In vivo experiments demonstrated that SIRT7 knockout exacerbated thrombocytopenia and further disrupted Th17/Treg homeostasis in murine models.

Conclusion

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.

目的Th17/Treg细胞失衡是免疫性血小板减少症（ITP）的重要致病机制；然而，潜在的监管机制仍然知之甚少。失调的琥珀酰化与疾病的发生和发展有关。因此，本研究旨在探讨琥珀酰化在ITP中调节Th17/Treg平衡的作用，并阐明相关的分子途径。方法采集ITP患者全血及小鼠模型。流式细胞术定量Treg和Th17细胞的频率。通过酶联免疫吸附法、实时定量聚合酶链反应和免疫印迹法分析Treg-和th17相关生物标志物。通过免疫共沉淀法、免疫荧光法和免疫印迹法评估SIRT7与STAT3琥珀酰化之间的调控关系。结果ITP患者表现出Th17/Treg比值升高，总体琥珀酰化水平升高，SIRT7表达降低。SIRT7的过表达在体外恢复了Th17/Treg失衡。机制上，SIRT7过表达抑制STAT3琥珀酰化在K573，从而抑制STAT3活性和下游信号传导。相反，STAT3的强制表达抵消了SIRT7过表达对Th17/Treg动态的影响。体内实验表明，SIRT7敲除加重了小鼠模型中的血小板减少症，并进一步破坏了Th17/Treg稳态。结论SIRT7通过STAT3去琥珀酰化，维持Th17/Treg平衡，从而减缓ITP进展。这些发现突出了SIRT7作为ITP治疗的潜在治疗靶点，为自身免疫性疾病中免疫失调的表观遗传调控提供了新的见解。

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引用次数: 0

Engineered iPSC-derived natural killer cells: recent innovations in translational innate anti-cancer immunotherapy 工程ipsc衍生的自然杀伤细胞：翻译先天抗癌免疫治疗的最新创新

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-07-10 DOI: 10.1002/cti2.70045

Jane Sun, Melissa Elliott, Fernando Souza-Fonseca-Guimaraes

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 in vitro and in vivo, achieved through genetic modification of iPSCs, as well as recent related clinical trials.

自然杀伤（NK）细胞越来越被认为是一种有效的肿瘤杀灭剂，可用于癌症免疫治疗。它们对肿瘤细胞具有先天的细胞毒性，并且降低了引起移植或患者毒性问题的风险，使它们成为探索同种异体过继细胞免疫疗法的有价值的选择。然而，从外周血中获取NK细胞在可扩展性、一致性和可变性方面存在挑战。诱导多能干细胞（iPSCs）正在成为一种具有高度控制过程的创造特定细胞的平台，为细胞治疗提供了一种共同的细胞来源，并提供了一种有前途的取之不尽的转基因NK细胞来源。本文综述了在特定培养系统中生成ipsc衍生NK细胞领域的最新进展，以及遗传修饰以改善iPSC-NK细胞治疗的进展。我们进一步讨论了iPSC库的发展，并研究了这些细胞在下一代免疫疗法中的潜力。最后，我们总结了ipsc衍生的NK （iNK）细胞在体外和体内的癌症靶向、扩增、持久性和细胞毒性功能方面的改进，这些改进是通过ipsc的遗传修饰以及最近的相关临床试验实现的。

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引用次数: 0

Data standards for single-cell RNA-sequencing of paediatric cancer 儿童癌症单细胞rna测序数据标准

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-07-10 DOI: 10.1002/cti2.70044

Xiaohan Xu, John Saxon, Megan Sioe Fei Soon, Colin YC Lee & Zewen Kelvin Tuong

Correction to: Clin Transl Immunol 2025; 14: e70033. https://doi.org/10.1002/cti2.70033

There is an error within a sentence within the first paragraph of the ‘Lack of important annotations’ section, as follows:

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 3d).

This should have read:

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 3d).

The authors apologise for this error.

许晓涵，John Saxon, Megan Sioe Fei Soon, Colin YC Lee &；纠正：临床Transl Immunol 2025；14: e70033。https://doi.org/10.1002/cti2.70033There是“缺乏重要注释”部分第一段中的一个句子中的错误，如下所示：此外，惊人的83%的数据集没有提供每个患者样本的足够临床特征（例如性别、年龄、疾病分期和治疗史）（图3d）。此外，17%的数据集没有提供每个患者样本的足够临床特征（如性别、年龄、疾病分期和治疗史）（图3d）。作者为这个错误道歉。

引用次数: 0

The role of immunochemotherapy maintenance in metastatic nasopharyngeal carcinoma: insights from a cohort study in an endemic region 免疫化疗维持在转移性鼻咽癌中的作用：来自一个流行地区队列研究的见解

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-07-02 DOI: 10.1002/cti2.70043

Zhuoying Luo, Yue Xia, Yuping Zhao, Haoyang Huang, Ying Deng, Zejiang Zhan, Yingying Huang, Xun Cao, Xi Chen, Jiayu Zhou, Chixiong Liang, Weixiong Xia, Liangru Ke, Xuehua Wei, Jinling Duan, Xing Lv, Hu Liang

Objectives

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.

Methods

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.

Results

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, P = 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, P = 0.005) or with elevated premaintenance Epstein–Barr virus (EBV) DNA levels (HR 0.063, 95% CI 0.007–0.548, P = 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.

Conclusions

Combined maintenance therapy with anti-PD-1 antibodies and capecitabine may be a feasible treatment strategy for mNPC patients.

目的姑息性化疗后转移性鼻咽癌（mNPC）的发病率和死亡率较高。虽然维持治疗显示出良好的潜力，但最佳策略仍未确定。本研究旨在评价免疫化疗维持治疗mNPC患者的疗效。方法本队列研究使用前瞻性维护的数据库，评估卡培他滨和抗pd -1抗体联合维持治疗mNPC患者的疗效。主要终点是无进展生存期（PFS），次要终点包括总生存期和安全性。并进行分层分析和敏感性分析。该研究纳入了2018年至2023年在中山大学癌症中心接受治疗的300例mNPC患者。男性234例（78.0%），中位年龄45岁[四分位间距（IQR）： 36-54岁]。中位随访43.6个月（IQR: 31.8 ~ 57.8），联合维持较单药维持显著改善PFS[加权风险比（HR） 0.580, 95%可信区间（95% CI） 0.387 ~ 0.872, P = 0.009；创造价值,2.27]。分层分析显示，未接受过局部治疗的患者（HR 0.414, 95% CI 0.244 - 0.767, P = 0.005）或维持前eb病毒（EBV） DNA水平升高的患者（HR 0.063, 95% CI 0.007-0.548, P = 0.012）维持免疫化疗的疗效增强。卡培他滨与抗pd -1单药组间PFS无显著差异。值得注意的是，联合治疗的PFS明显长于单药治疗。联合维持组和单药组的安全性相似。结论抗pd -1抗体联合卡培他滨维持治疗可能是mNPC患者的一种可行的治疗策略。

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引用次数: 0

Cellular hierarchy for understanding heterogeneity of acute myeloid leukaemia with t(8;21)/RUNX1-RUNX1T1 细胞层级对t(8;21)/RUNX1-RUNX1T1急性髓系白血病异质性的认识

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-07-02 DOI: 10.1002/cti2.70042

Yibo Wu, Xiaolin Yuan, Xiaoyu Lai, Lizhen Liu, Yue Liang, Lihong Ni, Luxin Yang, Shanshan Hu, Jimin Shi, Jian Yu, Yanmin Zhao, Weiyan Zheng, Jie Sun, Yuanyuan Zhu, Wenjun Wu, Zhen Cai, He Huang, Shanshan Pei, Yi Luo

Objectives

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.

Methods

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%, n = 166) or chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT; 41.72%, n = 141). Immunophenotypic profiling classified patients into progenitor subgroups: MPP (20.12%, n = 68), lymphoid-primed multi-potent progenitor (14.50%, n = 49), CMP (12.72%, n = 43), GMP (24.85%, n = 84) and GP/MP (10.36%, n = 35). Based on differentiation stage, patients were categorised as primitive (Immuno-Prim; 47.34%, n = 160) or monocytic (Immuno-Mono; 35.21%, n = 119).

Results

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.

Conclusions

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.

目的髓系恶性肿瘤的分化等级影响治疗效果和预后。急性髓性白血病（AML）伴t（8;21）是AML最常复发的遗传亚型之一，被认为是具有共同特征的独特实体。然而，临床结果仍然存在明显的异质性。本研究旨在探讨t(8;21) AML在特定分化阶段白血病骤停、基因组谱和临床结局之间的关系。方法我们对来自中国三个临床中心的338例t(8;21) AML患者进行了回顾性研究。患者接受单独化疗（49.11%,n = 166）或化疗后异体造血干细胞移植(alloo - hsct；41.72%, n = 141)。免疫表型分析将患者分为祖细胞亚组：MPP （20.12%, n = 68）、淋巴细胞引发的多能祖细胞（14.50%,n = 49）、CMP （12.72%, n = 43）、GMP （24.85%, n = 84）和GP/MP （10.36%, n = 35）。根据分化阶段，将患者分为原始（immune - prim）；47.34%, n = 160)或单核细胞(immune - mono；35.21%, n = 119)。结果与免疫- prim组相比，免疫- mono组的2年总生存期（OS）较低，2年累积复发发生率（CIR）较高。与没有突变的患者相比，KIT突变患者的2年OS较差，2年CIR较高。在同种hsct队列中，相对于免疫- prim组，免疫- mono组继续显示较低的2年OS和较高的2年CIR。基因突变（KIT除外）和染色体缺失均未显著影响OS或CIR。结论白血病分化阶段独立预测t(8;21) AML治疗后预后。在特定的髓细胞阶段的阻滞与基因畸变、临床表现、治疗反应和生存显著相关。

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引用次数: 0

Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity COVID-19后长期免疫变化及卡介苗接种和潜伏感染对疾病严重程度的影响

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology

Pub Date : 2025-06-27 DOI: 10.1002/cti2.70041

Kamila Bendíčková, Ioanna Papatheodorou, Gabriela Blažková, Martin Helán, Michaela Haláková, Petr Bednář, Erin Spearing, Lucie Obermannová, Julie Štíchová, Monika Dvořáková Heroldová, Tomáš Tomáš, Roman Panovský, Vladimír Šrámek, Marco De Zuani, Marcela Vlková, Daniel Růžek, Marcela Hortová-Kohoutková, Jan Frič

Objectives

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.

Methods

We conducted a prospective analysis of patients who recovered from mild/severe/critical COVID-19 (n = 97, 3–17 months after COVID-19) and sepsis patients (n = 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-Toxoplasma gondii/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.

Results

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.

Conclusion

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.

在COVID-19大流行几年后，SARS-CoV-2对免疫的影响以及通过训练免疫接种卡介苗的潜在保护作用仍是一个研究课题。本研究旨在确定SARS-CoV-2对免疫细胞的长期影响，以及卡介苗接种、潜伏感染与COVID-19严重程度和败血症进展之间的关系。方法前瞻性分析轻/重/危重型COVID-19患者（n = 97， COVID-19后3-17个月）和败血症患者（n = 64）。首先，我们评估了COVID-19及其严重程度对免疫细胞频率和功能标志物表达的影响。此外，我们分析了血浆抗刚地弓形虫/巨细胞病毒/卡介苗抗体滴度及其与COVID-19严重程度和败血症结局的关系。为了检测单核细胞对继发性攻击的反应，我们用SARS-CoV-2和LPS刺激从COVID-19恢复期患者、卡介苗接种者和未接种者中分离的单核细胞。结果无论疾病严重程度如何，covid -19后患者均表现出免疫失调，其特征是髓细胞（CD39、CD64、CD85d、CD11b）和淋巴样细胞（CD39、CD57、TIGIT）的活化和功能标志物表达改变。引人注目的是，与其他严重程度组相比，危重后的COVID-19患者CD8+ T细胞中CD57的表达升高。观察到bcg血清阳性的COVID-19/败血症患者预后改善的趋势，尽管这可能与组间年龄差异相混淆。相反，单核细胞对刺激的反应似乎不受COVID-19严重程度的影响。结论这些发现突出了COVID-19后患者免疫细胞的长期改变，强调了COVID-19对免疫功能的实质性影响。

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引用次数: 0