Frontiers in Immunology最新文献

{"title":"Editorial: Community series in the role of monocytes/macrophages in autoimmunity and autoinflammation, volume II.","authors":"Naoki Iwamoto, Atsushi Kawakami, Sachiko Miyake, Keishi Fujio","doi":"10.3389/fimmu.2025.1699650","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1699650","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1699650"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206277","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":"Deciphering the lactylation landscape in glioma: a novel gene signature predicts patient survival and immunotherapy sensitivity.","authors":"Xiaolong Tang, Yi Liu, Congying Yang, Honglan Zhang, Gongming Zhang, Qiao Wang, Sujie Jiang, Xuzhu Gao, Yongshuo Liu, Yanbin Dong","doi":"10.3389/fimmu.2025.1664347","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1664347","url":null,"abstract":"<p><strong>Background: </strong>Glioma, the most prevalent primary brain tumor, takes advantage of lactylation, a metabolic modification linked to tumor behavior and clinical outcomes. Despite its significance, the role of lactylation in the pathogenesis and prognosis of glioma remains underexplored. This study established a lactylation-derived molecular signature to predict survival and response to immunotherapy in glioma.</p><p><strong>Methods: </strong>Leveraging the TCGA glioma cohort, we established a lactylation-related gene (LRG) signature <i>via</i> LASSO and Cox regression analyses, and its prognostic value was validated in independent cohorts. We comprehensively characterized the associations between the LRGs signature and clinicopathological features, tumor immunity (immune infiltration and response to immunotherapy), genomic instability (mutational burden and heterogeneity), tumor stemness, and therapeutic vulnerability. <i>In vitro</i> validation of the oncogenicity of HSPE1 was conducted using the CCK-8, colony formation, transwell, and apoptosis assays in U87 and U251 glioma cells.</p><p><strong>Results: </strong>A four-gene lactylation signature (KIF2C, CALD1, HSPE1, and IFI16) was identified. Elevated LRGs score were correlated with advanced tumor grade, poor prognosis, and reduced response to immunotherapy. Patients in the LRGs-high group exhibited adverse clinicopathological features, including advanced age, higher WHO grade, IDH wild-type status, and 1p/19q non-codeletion. The nomogram model based on the LRGs score exhibited robust prognostic accuracy (C-index = 0.860). LRGs-related genes were enriched in immune regulatory pathways, such as cytokine signaling and interferon-γ response pathways. The LRGs-high group displayed increased infiltration of immunosuppressive cells, such as M2 macrophages, MDSCs, and CAFs, and distinct genomic instability profiles. Crucially, HSPE1 knockdown significantly suppressed the proliferation and invasion of glioma cell lines.</p><p><strong>Conclusions: </strong>We defined a novel LRGs signature integrating metabolic and immune dysregulation in glioma. This signature served as an independent predictor of prognosis and immunotherapy. Furthermore, we identified HSPE1 as a critical driver of glioma progression.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1664347"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206308","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":"No evidence of MMR induced trained immunity to prevent SARS COV2: results from a multi-centre RCT.","authors":"Sinead Delany-Moretlwe, Hakim-Moulay Dehbi, Izukanji Sikazwe, George Kyei, Kwadwo Koram, Erik Dubberke, Noluthando Mwelase, Dominic Hague, Linda-Gail Bekker, Linda Yun, Annalene Nel, Leon du Toit, Bruce Biccard, Katherine Gill, Chikumbutso Chipeta, Kathryn T Mngadi, Limakatso Lebina, Reshmi Dassaye, Villeshni Asari, Samantha H Fry, Edwin Turton, Khatija Ahmed, Kwadwo Kusi, Susan Adu-Amankwah, Roma Chilengi, Joyce Chinyama Chilekwa, Laurence Lovat, Dermot McGuckin, Emilia Caverly, Mary Politi, Ben Swan, Anne DeSchryver, Sherry McKinnon, Ananya Gupta, Gemma Jones, Nicholas Freemantle, Shabaana Khader, Helen Rees, Mihai G Netea, S Ramani Moonesinghe, Michael S Avidan","doi":"10.3389/fimmu.2025.1588190","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1588190","url":null,"abstract":"<p><strong>Background: </strong>Measles-containing vaccines (MCV), by training innate immune cells, are hypothesized to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19).</p><p><strong>Methods: </strong>In this international, double-blind, placebo-controlled trial, we randomly assigned adults, 18 years and older, to receive MCV or saline. The primary outcome was polymerase chain reaction (PCR) confirmed symptomatic COVID-19, up to 60 days after intervention. Secondary outcomes were PCR-confirmed symptomatic COVID-19 and serologically confirmed SARS-CoV-2 infection, up to 150 days after intervention.</p><p><strong>Results: </strong>Of 3411 randomised participants, the modified intention-to-treat population included 1607 in the MCV and 1545 in the saline group. The estimated risk of symptomatic COVID-19 by 60 days was 1.5% in the MCV and 1.2% in the saline group (risk difference, 0.3 percentage points, 95% CI, -0.5 to 1.1; p=0.52). At 150 days, these percentages were 4.1% (65/1585) and 4.1% (64/1544) in the MCV and saline groups, respectively (risk difference, 0.04 percentage points, 95% CI, -1.4 to 1.3; p=0.95). Based on serology results available at 0 and 150 days, 10.6% (100/945) of participants in the MCV and 10.3% (98/951) in the saline group had infection with SARS-CoV-2 over the course of the trial (risk difference, 0.3 percentage points, 95% CI, -2.6 to 3.1; p=0.84). Three patients were hospitalised with COVID-19 disease in the MCV and one in the saline group.</p><p><strong>Conclusions: </strong>Administering MCVs to stimulate trained immunity did not prevent COVID-19 or SARS-CoV2 infection. Stimulating trained immunity might not be useful for preventing respiratory illness during future pandemics.</p><p><strong>Clinical trial registration: </strong>https://clinicaltrials.gov/, identifier NCT04333732.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1588190"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206199","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":"Efficacy and safety of immune checkpoint inhibitors for advanced squamous non-small cell lung cancer: a systematic review and network meta-analysis.","authors":"Na Liu, Baowanze Zhang, Jiali He, Su Li","doi":"10.3389/fimmu.2025.1635757","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1635757","url":null,"abstract":"<p><strong>Objective: </strong>Significant efficacy heterogeneity exists between first- and second-line immunotherapy regimens for advanced squamous non-small cell lung cancer (SqNSCLC), but most regimens lack directly comparable clinical trial evidence, resulting in unclear prioritization. This analysis identifies optimal treatment strategies by evaluating differences in efficacy across immune checkpoint inhibitors (ICIs).</p><p><strong>Methods: </strong>We search through comprehensive databases, including PubMed, Embase, the Cochrane Library and the Clinical Trials Database. Traditional meta-analysis was done using Stata 15.0, while Bayesian-framework network meta-analysis was implemented with R's GEMTC package via Markov chain Monte Carlo simulation. Subgroup analyses were performed for different PD-L1 expression levels, number of treatments, ethnic groups, and smoking history.</p><p><strong>Results: </strong>We included 25 randomized controlled trials. Immune-related therapy can provide significant benefit relative to chemotherapy alone in advanced SqNSCLC. Compared with chemotherapy, except for ipilimumab+chemo [HR = 0.92,95%CI: (0.59-1.40)], atezolizumab+chemo [HR = 0.88, 95%CI: (0.56-1.40)], and durvalumab+chemo [HR = 0.84, 95% CI: (0.52-1.40)], durvalumab+ tremelimumab+chemo [HR = 0. 88, 95% CI: (0.54-1.40)], which significantly improved overall survival(OS). Cemiplimab [HR = 0.48, 95% CI: (0.34-0.67)] showed the best OS benefit. Compared with chemotherapy, all immunotherapies significantly improved progression-free survival (PFS) except for ipilimumab+chemo [HR = 0.87, 95% CI: (0.75-1.00)]. Sugemalimab+chemo provided the best survival benefit [HR = 0.34, 95% CI: (0.24-0.48)]. For PD-L1≥50% tumors, penpulimab showed excellent OS and PFS; for PD-L1 1-49% tumors, pembrolizumab+chemo and camrelizumab+chemo achieved the best OS and PFS, respectively; for PD-L1≥1% tumors, the tislelizumab+chemo and camrelizumab+chemo showed the best OS and PFS results, while for tumors with PD-L1 <1%, both nivolumab and serplulimab+chemo provided significant survival benefit. In Asian patients, patients treated with pembrolizumab or pembrolizumab + chemotherapy had favorable OS and PFS benefits. In non-Asian patients, there was also favorable OS and PFS benefit with cemiplimab. For former/current smokers, pembrolizumab+chemotherapy and camrelizumab+chemotherapy had significant OS and PFS benefit, but most immunotherapies did not improve OS and PFS in never smokers. Camrelizumab+chemo [OR = 3.5, 95% CI: (2.3-5.3)] had the best overall response rate (ORR) benefit. Ipilimumab+chemo had the highest incidence of adverse events (AEs) [OR = 2.0, 95% CI:(1.5-2.7)].</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero/, identifier CRD420251027447.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1635757"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206248","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":"Th17-associated cytokine gene hypomethylation reflects epigenetic dysregulation in graves' disease.","authors":"Yanfei Jiang, Kaida Mu, Zhaowei Huang, Xinwei Zhang, Yalin Wang, Wenyu Xu, Ronghua Song, Jinan Zhang","doi":"10.3389/fimmu.2025.1635883","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1635883","url":null,"abstract":"<p><strong>Introduction: </strong>Graves' disease (GD) is an organ-specific autoimmune disorder characterized by the presence of thyroid-stimulating hormone receptor autoantibodies (TRAb), leading to hyperthyroidism. While genetic and environmental factors contribute to GD pathogenesis, the role of epigenetic mechanisms, particularly in regulating Th17-associated cytokines, remains poorly understood.</p><p><strong>Methods: </strong>This study aimed to characterize the promoter methylation profiles of IL17, IL21, and IL22 in GD patients, evaluate their diagnostic potential, and explore correlations with clinical parameters. Targeted bisulfite sequencing was performed on peripheral blood mononuclear cells from 60 GD patients, including newly diagnosed and refractory individuals, and 60 matched healthy controls.</p><p><strong>Results: </strong>Significant hypomethylation at IL17, IL21, and IL22 promoter regions was observed in GD patients compared with controls (P = 2.5 × 10⁻⁷), with partial methylation restoration in refractory cases. Four specific CpG sites were identified as potential biomarkers, demonstrating good diagnostic performance with area under the curve (AUC) values exceeding 0.7, including chr4_123542549_R (AUC = 0.754) and chr12_68647247_R (AUC = 0.752). These sites were associated with elevated TRAb (OR = 4.00, P = 0.02) and FT4 levels (OR = 0.29, P = 0.02), respectively.</p><p><strong>Discussion: </strong>Our findings highlight Th17-related epigenetic dysregulation as a key feature of GD and support the potential of methylation markers for diagnostic and therapeutic monitoring applications.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1635883"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206186","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":"Exosomal FABP5 drives HCC progression via macrophage lipid metabolism and immune microenvironment remodeling.","authors":"Siyi Luo, Rui Tang, Ling Jiang, Qichi Luo, Junhao Fu, Bo Wu, Guowu Wang","doi":"10.3389/fimmu.2025.1644645","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1644645","url":null,"abstract":"<p><strong>Introduction: </strong>The progression of hepatocellular carcinoma (HCC) is intricately linked to complex interactions within the tumor microenvironment (TME), where the reprogramming of tumor-associated macrophages (TAMs) plays a pivotal role. However, how HCC cells regulate TAM metabolism and function via extracellular vesicles, such as exosomes, remains incompletely understood.</p><p><strong>Methods: </strong>We isolated exosomes from HCC cell lines and co-cultured them with macrophages. Using proteomics, lipid analysis, flow cytometry, and animal models, we evaluated the effects of exosomal FABP5 on macrophage polarization and lipid metabolism. The role of FABP5 in tumor progression was assessed via <i>in vivo</i> experiments.</p><p><strong>Results: </strong>This study reveals that HCC cells release fatty acid-binding protein 5 (FABP5) via exosomes, transferring it to TAMs, thereby inducing significant lipid metabolism reprogramming in macrophages. Mechanistically, exosomal FABP5 promotes lipid accumulation by activating the PPARγ signaling pathway, while potentially inhibiting the PPARα signaling pathway to reduce fatty acid oxidation, ultimately driving TAM polarization towards an M2 phenotype, characterized by increased secretion of immunosuppressive cytokines and a pro-tumor phenotype. Clinical data analysis indicates that high FABP5 expression in HCC tissues correlates with poor patient prognosis. In liver-specific FABP5 knockout mouse models and HCC xenograft models, FABP5 deletion significantly suppressed tumor growth, reduced M2-type TAM infiltration and lipid accumulation, and enhanced anti-tumor immune responses.</p><p><strong>Conclusion: </strong>These findings collectively uncover exosomal FABP5 as a key mediator of metabolic and immune communication between HCC and TAMs, promoting HCC progression by remodeling the tumor immune microenvironment, and suggest FABP5 as a potential therapeutic target for HCC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1644645"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206289","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":"Integrated multi-omics analysis of single-cell and spatial transcriptomics reveals distinct hpv-associated immune microenvironment features and prognostic signatures in cervical cancer.","authors":"Qiuyue Su, Xiangdong Tian, Fucheng Li, Xi Yu, Wenchen Gong, Yurong Chen, Jianan Wang, Siqi Yang, Shaojun Zhang, Qian Zhang, Shanshan Yang","doi":"10.3389/fimmu.2025.1612623","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1612623","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is a highly heterogeneous malignancy primarily driven by persistent infection with high-risk human papillomavirus (HPV). However, comprehensive analyses of heterogeneity in the immune microenvironment, particularly its spatial heterogeneity, between HPV-positive and HPV-negative CC remain limited, despite their critical clinical significance.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) sequencing on collected cervical cancer samples, integrating scRNA-seq, ST, and bulk RNA-seq to analyze distinct cell subtypes and characterize their spatial distribution. Multiplex immunofluorescence analysis was further utilized to validate HPV status-specific expression patterns. Cox regression and LASSO regression analyses were used to identify the prognostic signature on the TCGA dataset.</p><p><strong>Results: </strong>Through integrative analysis, we found that HPV-positive samples demonstrated elevated proportions of CD4⁺ T cells and cDC2s, whereas HPV-negative samples exhibited increased CD8⁺ T cell infiltration. In HPV-positive CC, epithelial cells acted as primary regulators of cDC2s via the <i>ANXA1</i>-<i>FPR1/3</i> pathway, with cDC2s subsequently modulating CD4⁺ T cells and interferon-related CD8⁺ T cell subtypes. In contrast, HPV-negative CC featured epithelial cells predominantly influencing monocytes and macrophages, which then interacted with CD8⁺ T cells. Notably, the <i>MDK</i>-<i>LRP1</i> ligand-receptor interaction emerged as a potential key mechanism for recruiting immunosuppressive cells into CC tumors, fostering an immunosuppressive microenvironment. Further, we constructed a risk score model based on an epithelial cell-related signature (ERS), which was significantly associated with patient survival. Noteworthy variations were observed in immune cell infiltration and immune microenvironment among distinct risk groups.</p><p><strong>Conclusion: </strong>Based on integrated multi-omics data, we precisely delineated the spatial transcriptional features of the tumor microenvironment in CC with different HPV statuses, including identifying distinct CD8⁺ T cell states and cell-cell communication. In addition, we developed an ERS closely associated with the immune environment and prognosis of CC. These results increase our understanding of the molecular mechanisms of cervical cancer under different HPV statuses and provide assistance for the precise treatment of cervical cancer.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1612623"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206364","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":"Mitochondrial transfer/transplantation in lung injury: mechanism, therapeutic potential, and clinical application.","authors":"Ling-Jie Wang, Peng-Fei Guo, SongOu Zhang, Sai Wang, Yi-Zhao Chen, Hong-Wang Yan, Xue-Lin Zhang","doi":"10.3389/fimmu.2025.1668281","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1668281","url":null,"abstract":"<p><p>Lung injury has become a critical clinical problem that urgently requires resolution due to its high morbidity, high mortality, and the limitations of existing treatment methods. Mitochondrial dysfunction, as the core mechanism of lung injury, promotes disease progression through energy metabolism imbalances, oxidative stress, and exacerbated inflammatory responses. Recent studies have found that intercellular mitochondrial transfer, acting as a \"transcellular rescue\" mechanism, can deliver functional mitochondria through pathways such as tunneling nanotubes, exosome. This process provides a novel approach to replenish energy for damaged cells, regulate inflammation, and repair tissues. In various lung injury models, mitochondrial transfer/transplantation has been shown to improve alveolar-capillary barrier function, reduce collagen deposition, inhibit the release of inflammatory factors, and restore mitochondrial membrane potential. This is particularly evident in conditions such as acute lung injury, pulmonary fibrosis, acute respiratory distress syndrome, and chronic obstructive pulmonary disease, where it shows significant therapeutic potential. The combination of diverse delivery methods and multi-source mitochondria provide a flexible strategy for clinical application. In summary, mitochondrial transfer, as an emerging intercellular communication and rescue mechanism, provides a promising new direction for the precision treatment of lung injury.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1668281"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205894","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 innate immune axis drives aortic dissection pathogenesis through inflammation and presents novel therapeutic targets.","authors":"Can Xu, Wenping Chen, Xinyu Nie, Rui Xu, Xingyue Feng, Zhifen Chen, Dongjin Wang","doi":"10.3389/fimmu.2025.1654622","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1654622","url":null,"abstract":"<p><p>Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency characterized by aortic layer separation and false lumen formation, with high mortality rates. Emerging evidence highlights the critical role of innate immunity in AD pathogenesis. Innate immune activation drives AAD progression through multiple mechanisms, including macrophage polarization (M1/M2 imbalance), neutrophil extracellular trap (NET) formation, and inflammasome activation. These processes amplify vascular inflammation via cytokine storms (IL-1β, IL-6, TNF-α) and oxidative stress, further promoting matrix metalloproteinase activation and smooth muscle cell phenotypic switching. The cGAS-STING pathway, triggered by mitochondrial DNA release, and TLR signaling act as central hubs connecting vascular injury to innate immune responses. This review synthesizes recent advances in the molecular mechanisms of AAD, focusing on aortic wall structural alterations, dysregulated signaling pathway, including TGF-β, Ang II, STING, and TLR cascades, and immune-inflammatory responses mediated by innate immune components. A deeper understanding of these innate immune components may lead to improved diagnostic biomarkers and targeted therapies for AAD management.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1654622"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206127","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":"Cell death mechanisms induced by gold nano-immunoconjugates-mediated photodynamic therapy against human oesophageal cancer stem cells.","authors":"Onyisi Christiana Didamson, Rahul Chandran, Heidi Abrahamse","doi":"10.3389/fimmu.2025.1585251","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1585251","url":null,"abstract":"<p><strong>Background: </strong>The current conventional therapy for oesophageal cancer is unable to effectively eliminate oesophageal cancer cells as a result of cancer stem cells (CSCs). These CSCs are the main factors responsible for treatment failure and tumour relapse associated with the present conventional oesophageal cancer therapy. A nano-immunoconjugate-based photodynamic therapy (PDT) proposes a potential approach to eliminate these CSCs efficiently.</p><p><strong>Method: </strong>In this study, we examined the mode of cell death action induced by the nano-immunoconjugates (NIC) mediated PDT comprising aluminium phthalocyanine tetra sulfonic acid chloride (AlPcS₄Cl), gold nanoparticles (AuNPs), and anti-CD271 antibody (AlPcS₄Cl-AuNPs-anti-CD271) against human oesophageal CSCs <i>in vitro</i>. The oesophageal CSCs were treated with NIC-mediated PDT, and their impacts on cell viability, oxidative stress, mitochondrial membrane, efflux of cytochrome c protein, caspase 3/7 activity, and cell death mechanism were examined. We further evaluated the effects of the treatment on the various phases of the cell cycle, DNA damage response pathways, and autophagy.</p><p><strong>Results: </strong>Findings from this study showed that NIC-mediated PDT significantly inhibited the cell growth of oesophageal CSCs, promoted reactive oxygen species (ROS) production and mitochondrial-mediated apoptotic cell death through the alteration of mitochondrial membrane potential Δψm, high efflux of cytochrome c protein, high activity of caspase 3/7 protease, and early apoptosis. Moreover, NIC-mediated PDT triggered cell cycle checkpoint activity in the G0/G1 phase, stimulated DNA damage response by increased DNA double-strand breaks (DSB) and ATM (ataxia-telangiectasia mutated) upregulation, and activated an autophagy action.</p><p><strong>Conclusion: </strong>The outcomes from this study showed the anticancer efficiency of gold nano-immunoconjugate-based PDT against human oesophageal CSCs. Overall, this study provides a rationale for gold nano-immunoconjugate-based PDT for a promising therapeutic application in the clinical treatment of oesophageal cancer.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1585251"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206234","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}