Frontiers in Immunology最新文献

{"title":"Clinical isolates of <i>Providencia rettgeri</i> and <i>Providencia Stuartii</i> evades neutrophil-mediated killing by subverting neutrophil-extracellular traps.","authors":"Joselyn E Castro, Federico Birnberg-Weiss, María J Toloza, Yasmín A Bertinat, Federico Fuentes, Agustín Peyloubet, Diego Faccone, Sonia A Gómez, Verónica I Landoni, Gabriela C Fernández","doi":"10.3389/fimmu.2025.1636387","DOIUrl":"10.3389/fimmu.2025.1636387","url":null,"abstract":"<p><strong>Introduction: </strong><i>Providencia rettgeri</i> (Pr) and <i>Providencia stuartii</i> (Ps) are clinically relevant opportunistic pathogens. They are resistant to several antibiotics including carbapenems. The immune response against these pathogens has never been investigated. Here, we aimed to evaluate whether neutrophils (PMN), key players against bacterial infections, were able to recognize and eliminate these bacteria.</p><p><strong>Methods: </strong>We measured PMN functions after challenge with selected clinical isolates of Pr and Ps, and used <i>Escherichia coli</i> ATCC (Eco), which fully activates PMN, for comparison. Bacterial survival was evaluated after exposure of PMN to bacteria for 1 or 3 h and colony formation units (CFU) were determined.</p><p><strong>Results: </strong>While PMN were able to partially contain Ps growth at 1 h, at 3 h both Pr and Ps were able to escape PMN-mediated killing compared to Eco, which was efficiently killed. Reactive oxygen species (ROS) generation was not induced by Pr or poorly induced by Ps, compared to Eco, but phagocytosis of Pr, Ps, and Eco was similar. Although Pr and Ps induced the release of double-stranded (d.s.) DNA early at 30 min (vital neutrophils extracellular traps or NETs), the release of late-induced NETs (3 h, suicidal NETs) was not observed, consistent with the absence of PMN death observed with Pr or Ps. In addition, Pr and Ps decreased suicidal NETs when Eco or PMA were used as inducers. This decrease was abolished by fixed bacteria, and was dependent on the release of a DNase activity. Twenty-four h after i.p. inoculation of mice with Pr, Ps or Eco, all bacteria induced migration of PMN to the peritoneum, but no PMN activation or NETs was observed in Pr or Ps-treated mice. When the distribution of bacteria in different organs was measured by CFU determination, Pr and Ps disseminated to the spleen and lungs, whereas Eco was exclusively present in the peritoneum.</p><p><strong>Discussion: </strong>The isolates used in this study of Pr and Ps are poor inducers of bactericidal PMN responses and display immune evasion strategies to subvert PMN-mediated killing. These evasion mechanisms, acting on degrading vital NETs and/or blocking the formation of suicidal NETs, would favor bacterial dissemination.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1636387"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328995","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":"Efgartigimod for patients with thymoma associated generalized myasthenia gravis during the perioperative period: a four-case report.","authors":"Liuli Ren, Ling Wei, Song Jiang, Hongru Li, Anguo Chen, Juanjuan Zhang","doi":"10.3389/fimmu.2025.1627584","DOIUrl":"10.3389/fimmu.2025.1627584","url":null,"abstract":"<p><strong>Background: </strong>Thymectomy is one of the main treatments for thymoma associated myasthenia gravis, but there is a risk of acute exacerbation of myasthenia gravis symptoms during the perioperative period of thymoma. Therefore, perioperative management is very important. We reported four cases of thymoma associated generalized myasthenia gravis who were treated with efgartigimod before and after the perioperative period. The myasthenic symptoms of the patients were quickly controlled before surgery, and the patients successfully completed the surgery without experiencing myasthenic crisis or respiratory failure after surgery.</p><p><strong>Case report: </strong>Four patients diagnosed with thymoma associated generalized myasthenia gravis were all acetylcholine receptor(AChR) antibody-positive, with case 2 also positive for Titin and anti-RyR antibodies. Prior to surgery, all patients exhibited varying degrees of myasthenic symptoms, with case 2 experiencing a myasthenic crisis induced by glucocorticoid pulse therapy before the operation. Admitted to our multidisciplinary treatment group for myasthenia gravis, all four patients received 1 to 2 treatments with efgartigimod before thymoma surgery, which led to an improvement in myasthenia symptoms and a significant reduction in MG-ADL and QMG scores. All four patients underwent video-assisted thoracoscopic mediastinal tumor resection under general anesthesia, followed by the 3rd to 4th treatments with efgartigimod postoperatively, with no perioperative myasthenic crisis occurring in any of the patients. Apart from case 1, who developed a new pulmonary infection postoperatively and experienced a temporary fluctuation in myasthenia symptoms, the other three patients had no severe complications. Follow-up visits at one month and three months postoperatively showed that three of the patients achieved minimum symptom expression (MG-ADL score ≤1).</p><p><strong>Discussion: </strong>Efgartigimod provides new insights into the perioperative management of thymomas in patients with thymoma associated generalized myasthenia gravis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1627584"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328985","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":"Notch signalling in T cells: bridging tumour immunity and intratumoral cellular crosstalk.","authors":"Jasmine Sultana, Pritha Roy Choudhury, Saurav Bera, Mohona Chakravarti, Aishwarya Guha, Prodipto Das, Juhina Das, Gayatri S Iyer, Anirban Sarkar, Sukanya Dhar, Nilanjan Ganguly, Rathindranath Baral, Anamika Bose, Saptak Banerjee","doi":"10.3389/fimmu.2025.1659614","DOIUrl":"10.3389/fimmu.2025.1659614","url":null,"abstract":"<p><strong>Background: </strong>Notch receptor-ligand interaction is ubiquitous and fundamental for coordinating cellular differentiation and determining cell fate for the development of various tissues and organs. Aberrant mutations in the Notch cascade result in various pathophysiological disorders, including cancer. Diverse aspects of carcinogenesis regulated by Notch include the shaping of anti-tumour T-cell immunity through antigen-presenting cell (APC)-T cell interaction and effector functions.</p><p><strong>Chief content: </strong>Notch depends on juxtacrine and paracrine signalling to influence intercellular communications in the tumour microenvironment. Several preclinical and clinical studies have revealed Notch as a bi-effector molecule, which has a differential effect depending on the immune contexture of the tumour microenvironment. The Notch cascade serves as an effective therapeutic target in preventing off-target cell death and promoting tumour-specific T-cell priming.</p><p><strong>Conclusion: </strong>This review revolves around Notch crosstalk with respect to the interaction between T-cell populations and other intratumoral cellular components, including professional antigen-presenting cells like dendritic cells, macrophages, B cells, immunosuppressive myeloid-derived suppressor cells, and cancer stem cells. It also summarizes the impact of targeting Notch signalling within intratumoral T cells in combination with traditional oncotherapies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1659614"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328916","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":"From promise to practice: evaluating the clinical impact of FcRn inhibition in IgG-mediated autoimmune rheumatic diseases.","authors":"Chu Wei Yang, Ting Xia, Qing Tan, Li Gang Jie, Ai Ju Lou, Xiao Xiao Li, Maierhaba Maitiyaer, Wen Hui Huang, Yu Zheng, Shui Lian Yu","doi":"10.3389/fimmu.2025.1656937","DOIUrl":"10.3389/fimmu.2025.1656937","url":null,"abstract":"<p><p>The neonatal Fragment Crystallizable receptor (FcRn) plays a central role in maintaining immunoglobulin (Ig) G homeostasis by protecting IgG from lysosomal degradation and regulating its transcytosis. In recent years, pharmacological inhibition of FcRn has emerged as a promising therapeutic strategy for IgG-mediated aumhctoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, anti-Neutrophil Cytoplasmic Antibodies (ANCA) -associated vasculitis, and others. By accelerating the catabolism of circulating IgG, FcRn inhibitors effectively reduced pathogenic autoantibody levels without broadly suppressing other immune components. Several FcRn-targeting agents, such as efgartigimod, rozanolixizumab, and nipocalimab, have demonstrated favorable safety and efficacy profiles in clinical trials and are now approved or under investigation for multiple indications. This review also explored personalized therapeutic approaches, combination strategies, and the future landscape of FcRn-targeted drug development. While FcRn inhibition offered a paradigm shift in managing antibody-driven diseases, long-term safety and patient stratification remain key challenges for future research.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1656937"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328288","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":"Dual roles of <i>in situ</i> generated HSP70 in antigen delivery and immunoregulation.","authors":"Xinliang Kang, Zhuofan Li, Jayachandra Reddy Nakkala, Yibo Li, Labone Akter, Yiwen Zhao, Xinyuan Chen","doi":"10.3389/fimmu.2025.1638948","DOIUrl":"10.3389/fimmu.2025.1638948","url":null,"abstract":"<p><strong>Introduction: </strong>Extracellular release of inducible HSP70 spurred interests to explore its potential interactions with innate immune systems. Both pro- and anti-inflammatory roles have been reported though the immunostimulatory roles were largely disputed due to the likely use of contaminated HSP70. The anti-inflammatory roles inspired the exploration of HSP70 to treat autoimmune diseases by suppressing pathological inflammatory responses. Besides immunomodulation, HSP70 has been explored as tumor vaccine carriers to elicit cytotoxic T lymphocyte responses due to its ability to deliver bound peptides to MHC I presentation pathway. With increasing understanding of the potential use of ex vivo prepared HSP70 in vaccination and therapy, the functions and potential applications of <i>in situ</i> induced HSP70 in antigen delivery and immunomodulation remain largely unexplored.</p><p><strong>Methods: </strong>This study utilizes physical radiofrequency adjuvant (RFA) to induce HSP70 synthesis accompanied with mild inflammation followed by intradermal injection of vaccine antigens into RFA-treated skin in murine models to explore its potential roles in antigen delivery and immunomodulation.</p><p><strong>Results: </strong>We found <i>in situ</i> induced HSP70 could bind intradermally injected model antigen ovalbumin and contribute to enhanced antigen uptake in skin and draining lymph nodes. HSP70 failed to induce dendritic cell maturation and rather suppressed RFA-induced TLR4/IRAK/NFκB activation and IL-6 expression.</p><p><strong>Discussion: </strong>These results indicate dual roles of <i>in situ</i> induced HSP70 in antigen delivery and immunoregulation at physiological conditions. These dual functions highlight opportunities to exploit endogenous HSP70 for both vaccine adjuvantation and immunomodulation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1638948"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328947","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":"Innate immunity of bile and cholangiocytes in primary biliary cholangitis.","authors":"Ran Chen, Yan Sun, Ying Hu, Wenlin Tai","doi":"10.3389/fimmu.2025.1655287","DOIUrl":"10.3389/fimmu.2025.1655287","url":null,"abstract":"<p><p>Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts. This review synthesizes current knowledge on the critical role of innate immunity, specifically involving cholangiocytes, bile components, and associated immune cells. Cholangiocytes function not only as passive targets but also as active immunomodulators through mechanisms including Toll-like receptor (TLR) signaling, antigen presentation, and immune cell recruitment. Dysregulated bile acid signaling via receptors like TGR5 disrupts immune homeostasis, while apoptosis of biliary epithelial cells releases antigens (e.g., PDC-E2), triggering aberrant innate and adaptive immune responses. Innate lymphoid cells (ILCs), natural killer (NK) cells, and macrophages exhibit altered frequencies and functions in PBC, driving chronic inflammation and fibrosis through cytokine cascades (e.g., IL-17, IFNγ) and interactions within the gut-liver axis. Furthermore, biliary microbiota dysbiosis exacerbates disease by promoting bacterial translocation, modifying bile acid metabolism, and activating innate immune pathways. Current clinical management with ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) primarily addresses cholestasis. However, the immunomodulatory effects of these agents remain constrained. Targeted therapeutic strategies addressing innate immune pathways-exemplified by RIPK2 (Receptor Interacting Serine/Threonine Kinase 2) inhibition, IL-1 blockade(Canakinumab), and T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) modulation-alongside cell-based interventions such as mesenchymal stem cell therapy, demonstrate considerable therapeutic potential. Advancing these modalities necessitates multidisciplinary integration to facilitate clinical translation. Additionally, Prognostic indices like the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) reflect systemic inflammation and correlate with disease progression. Achieving therapeutic precision requires deeper elucidation of the gut-biliary-immune axis, trained immunity mechanisms, and cholangiocyte senescence, paving the way for targeted interventions in PBC. Establishing a comprehensive treatment burden assessment system is imperative to facilitate the transition from investigational platforms to clinical care.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1655287"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328912","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":"Premature renal epithelial cell senescence promoted by LXN/Rps3/p53 signaling pathway activation increases calcium oxalate crystal deposition by altering macrophage polarization.","authors":"Maolin Chu, Suna Jiang, Jiawei Xue, Wenjing Li, Guanhua Jing, Hongying Li, Juan Zhang, Wanhai Xu","doi":"10.3389/fimmu.2025.1658989","DOIUrl":"10.3389/fimmu.2025.1658989","url":null,"abstract":"<p><strong>Introduction: </strong>Premature senescence of renal tubular epithelial cells (RTECs) can be caused by oxidative stress related to calcium oxalate (CaOx) kidney stones (KSs), but the role and mechanisms of cellular senescence of RTECs in the pathogenesis of kidney stones have not been fully determined. Macrophages, the most prevalent leucocyte found in nephrolithiasis, have been implicated in the pathogenesis of kidney stones.</p><p><strong>Methods: </strong>Using oxalate (Ox) induction to simulate the hyperoxaluria microenvironment in vivo, fisetin was administered to human renal proximal tubular epithelial cells (HK-2 cells). The senescence of HK-2 cells was evaluated by detecting SA-β-gal staining, expression of senescence markers p16 and p53, and levels of senescence-associated secretory phenotype (SASP) molecules. THP-1 cells were differentiated into macrophages (M0-MΦs) using PMA induction, and macrophages in different polarization states (M1-like phenotype, M2-like phenotype) were treated with the supernatant from HK-2 cell culture. siRNA gene knockdown technology was applied to evaluate the activity of the LXN/Rps3/p53 pathway during oxalate-induced senescence in HK-2 cells. A rat model of calcium oxalate crystal-induced kidney injury was established, and the rats were divided into following groups: PBS, oxalate, oxalate + fisetin, oxalate + transfection with LXN-knockdown adeno-associated virus (AAV-shLXN), and oxalate + fisetin + AAV-shLXN, Histological assessment was performed using HE staining and Von Kossa staining of kidney tissues. The expression levels of LXN, Rps3, p53, iNOS, and CD163 in renal tissues were evaluated by immunohistochemical staining.</p><p><strong>Results: </strong>The onset of RTEC senescence was increased after treatment with oxalate, and the increase in RTEC senescence was reduced by fisetin treatment. Interestingly, the changes in proinflammatory M1-like phenotype polarization induced by culture medium from HK-2 cells treated with Ox+/-fisetin were consistent with the proportion of senescent HK-2 cells cultured. Furthermore, reducing cellular LXN/Rps3/p53 signaling significantly decreased SASP factors in the culture medium and simultaneously abolished M1-like phenotype macrophage polarization. More importantly, silencing renal LXN reduced RTEC senescence and M1-like phenotype macrophage polarization and consequently decreased intrarenal CaOx crystal deposition in a rat kidney stone model.</p><p><strong>Discussion: </strong>Our results demonstrate that kidney macrophage phenotype changes are related, at least in part, to RTEC senescence, and a strategy to modulate the cellular senescence of RTECs is promising as a new target for immunotherapy to treat nephrolithiasis and other age-related diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1658989"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328919","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":"3KO-NSCs ameliorate behavioral deficits and modulate gut microbiota in a VPA-induced C57BL/6 mouse model of autism.","authors":"Caixia Wu, Xianjie Li, Han Wang, Xiaoya Yang, Zhaoming Liu","doi":"10.3389/fimmu.2025.1680179","DOIUrl":"10.3389/fimmu.2025.1680179","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) involves complex neurological and gastrointestinal pathophysiology. Existing therapies rarely address the gut-brain axis connection. This study evaluated the therapeutic potential of immune-evasive human induced pluripotent stem cell-derived neural stem cells (3KO-NSCs) in a mouse model of ASD.</p><p><strong>Methods: </strong>We used a valproic acid (VPA)-induced ASD model in C57BL/6 mice. Mice received systemic administration of 3KO-NSCs. Assessments included behavioral assays (social interaction, repetitive behaviors), hippocampal cytokine profiling (IL-6, TNF-α), 16S rRNA sequencing for gut microbiota analysis, immunohistochemistry (Iba1⁺ microglia), and ultrastructural synaptic analysis.</p><p><strong>Results: </strong>3KO-hiPSC-NSC treatment significantly ameliorated VPA-induced ASD-like behaviors. It reduced hippocampal neuroinflammation (decreased IL-6 and TNF-α) and attenuated microglial overactivation (reduced Iba1+ cells), correcting synaptic pruning abnormalities. Concurrently, treatment restored gut microbiota diversity (increased Shannon index), enriching Bacteroides and reducing pro-inflammatory Proteobacteria.</p><p><strong>Conclusions: </strong>3KO-NSCs exert dual therapeutic effects by mitigating central neuroinflammation and rebalancing gut microbiota. This provides the first direct evidence that stem cell therapy can modulate the gut-brain axis to treat ASD, positioning 3KO-NSCs as a novel bifunctional therapeutic strategy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1680179"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328844","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":"Artificial intelligence-driven analysis of antibody and nucleic acid biomarkers for enhanced disease diagnostics.","authors":"Zihan Liu, Feng Zhu, Mei Zhang","doi":"10.3389/fimmu.2025.1633989","DOIUrl":"10.3389/fimmu.2025.1633989","url":null,"abstract":"<p><strong>Introduction: </strong>The rapid evolution of artificial intelligence (AI) technologies has catalyzed a paradigm shift in the landscape of biomarker-driven disease diagnostics, particularly in the context of integrating antibody and nucleic acid indicators. Within this transformative setting, AI offers unprecedented potential for decoding complex molecular interactions across heterogeneous data sources, facilitating early and precise disease identification. However, the effective deployment of AI in this domain mandates enhanced model interpretability, robust cross-domain generalization, and biologically grounded learning strategies-challenges that resonate deeply with contemporary research focused on antibody and nucleic acid diagnostics.</p><p><strong>Methods: </strong>Traditional methodologies for biomarker discovery-such as linear regression, random forests, and even standard deep neural networks-struggle to accommodate the multi-scale dependencies and missingness typical of omics datasets. These models often lack the structural alignment with biological processes, resulting in limited translational utility and poor generalization to new biomedical contexts. To address these limitations, we propose a novel framework that integrates a biologically informed architecture, BioGraphAI, and a semi-supervised learning strategy, adaptive contextual knowledge regularization (ACKR). BioGraphAI employs a hierarchical graph attention mechanism tailored to capture interactions across genomic, transcriptomic, and proteomic modalities. These interactions are guided by biological priors derived from curated pathway databases.</p><p><strong>Results: </strong>This architecture not only supports cross-modal data fusion under incomplete observations but also promotes interpretability via structured attention and pathway-level embeddings. ACKR complements this model by incorporating weak supervision signals from large-scale biomedical corpora and structured ontologies, ensuring biological plausibility through latent space regularization and group-wise consistency constraints.</p><p><strong>Discussion: </strong>Together, BioGraphAI and ACKR represent a step toward overcoming critical barriers in biomarker-driven disease diagnostics. By grounding computational predictions in biological priors and enhancing interpretability through structured embeddings, this framework advances the translational applicability of AI for early and precise disease identification.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1633989"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328878","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":"Single-cell and spatial transcriptomics integration: new frontiers in tumor microenvironment and cellular communication.","authors":"Wenxin Shi, Zhiqiang Zhang, Xiaotong Xu, Yanpeng Tian, Li Feng, Xianghua Huang, Yanfang Du, Zhongkang Li","doi":"10.3389/fimmu.2025.1649468","DOIUrl":"10.3389/fimmu.2025.1649468","url":null,"abstract":"<p><p>Single-cell RNA sequencing (scRNA-seq) has emerged as an advanced biological technology capable of resolving the complexity of cancer landscapes at single-cell resolution. Spatial transcriptomics(ST), as an innovative complementary approach, effectively compensates for the lack of spatial information inherent in scRNA-seq data. This review explores the rapidly evolving integration of scRNA-seq and ST and their transformative role in deciphering the tumor microenvironment (TME). We highlight how these technologies jointly uncover cellular heterogeneity, stromal-immune interactions, and spatial niches driving tumor progression and therapy resistance. Moving beyond previous reviews, we emphasize emerging computational strategies for data integration-including deconvolution and mapping approaches-and evaluate their applications in characterizing immune evasion, fibroblast diversity, and cell-cell communication networks. Ultimately, this review provides a forward-looking perspective on how spatial multi-omics are poised to advance precision oncology through spatially-informed biomarkers and diagnostic tools. We conclude that the full clinical potential of these technologies relies on closing the gap between analytical innovation and robust clinical implementation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1649468"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12528096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328920","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}