Frontiers in Immunology最新文献

{"title":"From density to spatial function: spatial multi-omics, composite biomarker design, and therapeutic engineering of tertiary lymphoid structures in solid tumors.","authors":"Xuchen Wang, Lin Lin","doi":"10.3389/fimmu.2026.1865949","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1865949","url":null,"abstract":"<p><strong>Background: </strong>Tertiary lymphoid structures (TLSs) have emerged as clinically relevant immune niches associated with improved survival and enhanced response to immune checkpoint inhibitors across multiple solid tumors. However, translational evaluation remains dominated by density-based scoring, which inadequately captures the functional heterogeneity of histologically similar lymphoid aggregates. This review synthesizes recent advances in spatial biology that support a shift from counting TLSs to interpreting them as spatially organized immune microenvironmental units embedded within local tumor ecosystems.</p><p><strong>Main body: </strong>Evidence from spatial transcriptomics, multiplexed imaging, single-cell profiling, computational pathology, and spatial-proteomic approaches converges on four coupled requirements for productive TLS function: stromal licensing through lymphotoxin-dependent chemokine circuits, vascular competence mediated by specialized high endothelial venules, helper T-cell programs that bridge follicular and cytotoxic immunity, and a permissive metabolic context that enables maturation. Spatial studies further show that regulatory infiltration, suppressive plasma-cell programs, and metabolic disruption can decouple structural presence from effective antitumor immunity. Across tumor types, these insights indicate that biomarker performance improves when TLS density is integrated with maturity, anatomical location, HEV coupling, immune composition, and treatment context rather than used as a standalone metric. We further discuss how spatial analyses reveal actionable pathways for inducing or reprogramming TLSs and outline a staged, module-matched composite biomarker workflow combining digital pathology, targeted multiplexed imaging, and focused molecular or metabolic augmentation.</p><p><strong>Conclusions: </strong>TLSs should be regarded as spatially organized, functionally heterogeneous immune microenvironmental units rather than biologically equivalent lymphoid aggregates. A spatial-functional framework helps explain productive, arrested, and suppressive TLS states, provides a basis for next-generation composite biomarkers, and supports module-matched therapeutic strategies tailored to the stromal, vascular, helper-cell, or metabolic bottleneck limiting TLS function in individual tumors. The immediate next step is prospective validation of a minimal TLS panel across defined treatment contexts.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1865949"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223884","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":"Cathepsin S: a double-edged protease in barrier damage, neuroimmune inflammation, and tissue repair, with implications for dermatology.","authors":"Haien Wu, Fang Su, Chang Li, Chunfang Guo, Zhen Wang","doi":"10.3389/fimmu.2026.1937685","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1937685","url":null,"abstract":"<p><p>Cathepsin S (CTSS) is a lysosomal cysteine protease traditionally recognized for its role in invariant-chain degradation and major histocompatibility complex class II antigen presentation. However, unlike many lysosomal cathepsins, CTSS remains active at neutral or mildly acidic pH, enabling proteolytic functions at the cell surface and within extracellular inflammatory microenvironments. This property makes CTSS particularly relevant to skin biology, where barrier disruption, immune activation, neuroimmune signaling, extracellular matrix remodeling, angiogenesis, fibrosis, tumor progression, and tissue repair often coexist. This review summarizes the context-dependent and double-edged role of CTSS in inflammation and repair, with emphasis on its dermatological relevance. CTSS can promote pathogenic inflammation through multiple mechanisms, including regulation of antigen presentation, activation of cytokine pathways such as IL-36γ, degradation of antimicrobial and barrier-associated proteins, activation of protease-activated receptor 2, cleavage of fractalkine/CX3CL1, and modulation of neuroimmune circuits involved in itch and pain. These mechanisms implicate CTSS in inflammatory and immune-mediated dermatoses such as psoriasis, atopic dermatitis, vitiligo, rosacea, seborrheic dermatitis, and cutaneous lupus-related autoimmunity. CTSS may also contribute to extracellular matrix turnover, fibroblast activation, vascular remodeling, skin aging, keloid formation, systemic sclerosis-associated fibrosis, and cutaneous melanoma progression. Conversely, CTSS is not uniformly pathogenic. In selected contexts, it may support macrophage, M2 polarization, matrix remodeling, wound repair, and inflammatory resolution. This duality suggests that the biological impact of CTSS depends on its timing, location, cellular source, substrate specificity, and disease stage. Recent pharmacological findings, including rebound CTSS activity and increased CTSS protein mass after repeated administration of a selective CTSS inhibitor, further indicate that simple systemic inhibition may be insufficient or potentially counterproductive. Therefore, CTSS should be viewed as a context-dependent protease switch rather than a universally harmful enzyme. A better understanding of its compartment-specific and stage-specific functions may help guide more selective therapeutic strategies, including local delivery, substrate-selective modulation, combination approaches, and disease-stage-adapted intervention. This framework may refine the development of CTSS-targeted therapies for skin diseases and skin-related immune disorders.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1937685"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223910","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":"Unlocking the therapeutic potential of traditional Chinese medicine in Crohn's disease: from multi-target mechanisms to clinical promise.","authors":"Meng'en Zhou, Yan Chen, Jie Hu, Xiutian Guo, Wenqi Jin","doi":"10.3389/fimmu.2026.1719353","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1719353","url":null,"abstract":"<p><p>Crohn's disease (CD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract with an unclear etiology. Current Western therapies, including 5-aminosalicylates, corticosteroids, biologics, and immunomodulators, often fail to maintain sustained remission and are associated with significant adverse effects and high recurrence rates following drug withdrawal. Traditional Chinese medicine (TCM) has shown potential in alleviating CD symptoms through multi-target and multi-pathway mechanisms. Thus, this review aims to systematically summarize recent advances in understanding the mechanisms by which TCM intervenes in CD, focusing mainly on: regulating immune balance (including modulation of Th1/Th2, Th17/Treg, and M1/M2 macrophage polarization), attenuating inflammatory cascades (via NF-κB, MAPK, PI3K/AKT, and JAK/STAT pathways), reducing oxidative stress, regulating programmed cell death in intestinal epithelial cells (including apoptosis, pyroptosis, ferroptosis, and autophagic cell death), enhancing intestinal mucosal barrier integrity, and promoting restoration of intestinal microbial homeostasis. Furthermore, TCM combined with Western therapies may exert synergistic effects to improve clinical efficacy and reduce relapse risk. Future research could further integrate network pharmacology and multi-omics technologies to elucidate the molecular mechanisms of TCM more deeply, advancing precision therapeutics for CD.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1719353"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223854","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":"Correction: Neutrophil extracellular traps in asthma and chronic obstructive pulmonary disease: pathogenic roles, and therapeutic opportunities.","authors":"Xijie Zhang, Tobias Dallenga, Susanne Krauss-Etschmann","doi":"10.3389/fimmu.2026.1993356","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1993356","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2026.1919974.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1993356"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223856","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":"Supernatants from stored platelet concentrates modulate the inflammatory response in platelet-depleted blood ex vivo.","authors":"Linnea I Andersson, Dick J Sjöström, Nahreen Tynngård, Camilla Mohlin, Huy Quang Quach, Ivar Tjernberg, Sofia Ramström, Tom Eirik Mollnes, Per H Nilsson","doi":"10.3389/fimmu.2026.1928875","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1928875","url":null,"abstract":"<p><strong>Introduction: </strong>Platelets contain a wide range of bioactive mediators, many of which accumulate during storage of platelet concentrates and have immunomodulatory properties. Our objective was to investigate how mediators derived from stored platelet concentrates modulate the acute inflammatory response using an ex vivo model.</p><p><strong>Methods: </strong>Platelet-depleted whole blood from healthy donors (n=8) was supplemented with pooled platelet concentrate supernatants generated from six platelet concentrates sampled on storage days 1, 3, 5, and 7, and incubated with or without heat-inactivated <i>Escherichia coli</i> for four hours at 37 °C. Inflammatory responses were assessed by measuring complement activation, platelet-derived mediators, and cytokines.</p><p><strong>Results: </strong>In the absence of <i>E. coli</i>, addition of platelet concentrate supernatants increased the levels of 24 of 32 measured inflammatory mediators. In contrast, under <i>E. coli</i>-stimulated conditions, the supernatants increased 10 markers and attenuated 14 markers, including the key pro-inflammatory cytokines IL-1β, IL-6, and TNF. The attenuation of these cytokines ranged from 25-43%, whereas several other mediators were unchanged or increased. The majority of biomarkers showed limited differences across the investigated storage time points.</p><p><strong>Conclusions: </strong>Our findings demonstrate that soluble factors released from platelet concentrates can modulate inflammatory responses in platelet-depleted blood in an ex vivo setting, with context-dependent, bidirectional, and selective immunomodulatory effects.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1928875"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223863","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":"IL18BP links antigen processing and presentation programs to a dendritic cell-enriched immunoregulatory state in colorectal cancer.","authors":"Junyin Zheng, Guodong Guo, Yue Tian, Liqi Chen, Haoyun Xia, Yiqing Jiang, Dajia Lin, Hao Zhang, Nan Zhang, Chenshen Huang","doi":"10.3389/fimmu.2026.1973858","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1973858","url":null,"abstract":"<p><strong>Background: </strong>Antigen processing and presentation (APP) is required for tumor immune recognition, but its relationship with the immune landscape in colorectal cancer (CRC) remains incompletely defined. In this study, APP-related transcriptional programs were used as the starting point to identify immune-cell-associated biomarkers with prognostic and immunotherapeutic relevance in CRC.</p><p><strong>Methods: </strong>Six public CRC bulk cohorts were analyzed to define APP-related molecular states. Weighted gene co-expression network analysis and four machine-learning frameworks, including Boruta, LassoLR, Pamr, and XGBoost, were applied to prioritize genes linked to APP activity. Single-cell analysis was performed with an atlas of 121 samples and 169,427 cells to identify the cellular origin of the candidate gene. Immune infiltration, cancer-immunity-cycle activity, immune checkpoint blockade (ICB) response, predicted drug response, somatic mutation patterns, and <i>in vitro</i> function were then evaluated.</p><p><strong>Results: </strong>Two APP-associated patterns were identified and showed different survival outcomes and immune landscapes. Network- and machine-learning-based screening prioritized IL18BP as the main APP-associated candidate. Higher IL18BP expression was associated with longer survival and an immune-active phenotype, including stronger antigen-presentation signals, increased immune infiltration, checkpoint-related signatures, and cancer-immunity-cycle activation. Single-cell profiling showed that IL18BP was preferentially enriched in dendritic cells (DCs), linking the APP-derived bulk signature to a DC-centered immunoregulatory compartment. Across nine external ICB-treated cohorts, IL18BP showed response-classification performance. Drug-response prediction and somatic mutation analyses identified additional features associated with IL18BP-defined groups. In CRC cell lines, IL18BP knockdown increased proliferation, migration, and invasion.</p><p><strong>Conclusion: </strong>These findings identify IL18BP as a DC-enriched, APP-associated biomarker in CRC. By connecting APP programs in bulk tumors with DC-level expression patterns at single-cell resolution, this study positions IL18BP as an APP-associated marker of a DC-enriched immune state. These findings support further evaluation of IL18BP for prognostic and immunotherapy stratification in colorectal cancer but do not establish a causal APP-DC-IL18BP pathway.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1973858"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223999","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":"Identification of psoriasis-associated hub genes by integrated transcriptomics and machine learning.","authors":"Yaqi Zhao, Xiao Liang, Mingwei Tang, Lin Qiao, Wei Bai, Can Huang, Mengtao Li, Xiaofeng Zeng, Xiaomei Leng","doi":"10.3389/fimmu.2026.1937515","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1937515","url":null,"abstract":"<p><p>This study aims to systematically identify key hub genes in psoriasis pathogenesis through the integration of bioinformatics, machine learning and experimental validation methods. Four psoriasis microarray datasets were retrieved from the GEO database, with differentially expressed genes identified through comparative analysis. A dual machine learning approach screened core hub genes, whose expression levels and diagnostic efficacy were validated in an independent cohort. CIBERSORT was employed for immune cell infiltration analysis, whilst a multi-database approach constructed an mRNA-miRNA-lncRNA regulatory network. Molecular docking technology assessed interactions between the environmental pollutant bisphenol A, predicted drugs, and hub genes. Finally, an <i>in vitro</i> psoriasis model was established by stimulating HaCaT cells with the M5 cytokine mixture, with hub gene expression validated via RT-qPCR. Results show that 77 co-differentially expressed genes were identified in psoriasis. Machine learning screened five key hub genes: CARHSP1, HPSE, PCLAF, SERPINB4, and SPRR2C. These were significantly upregulated in the validation cohort and demonstrated strong discriminative value for distinguishing psoriatic lesional skin from paired non-lesional skin, rather than serving as standalone diagnostic biomarkers for psoriasis. Immune cell infiltration analysis revealed extensive associations with immune subpopulations including T cells and macrophages. Molecular docking computationally predicted a potential binding interaction between the environmental pollutant BPA and the hub gene HPSE, which awaits future experimental validation. Concurrently, Genistein and HPSE were suggested a potential interaction that awaits functional validation. <i>In vitro</i> experiments confirmed significant upregulation of HPSE, PCLAF, and SPRR2C mRNA levels in M5-induced psoriasis cell models. HPSE emerged as a multifunctional core gene associated with immune dysregulation. Molecular docking additionally predicted a potential interaction between the environmental pollutant BPA and HPSE; however, this interaction remains a computational hypothesis requiring experimental validation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1937515"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223970","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 application of Chicago classification 4.0 in esophageal motility disorders of scleroderma: a case-control study in China.","authors":"Yinghui Yang, Siwei Xie, Minyi Xu, Zhiming Lin, Yanli Zhang","doi":"10.3389/fimmu.2026.1962332","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1962332","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by multi-organ fibrosis and vasculopathy that frequently involves the esophagus. This study assessed esophageal motility disorders in patients with SSc using High-resolution manometry (HRM) and classified these disorders according to the Chicago Classification version 4.0, aims to investigate the associations between esophageal dysfunction and clinical phenotypes in Chinese SSc patients, while exploring potential modifications to enhance the applicability of the Chicago v4.0 protocol in SSc patients.</p><p><strong>Methods: </strong>We retrospectively identified SSc patients fulfilling 2013 ACR criteria who underwent HRM classified by Chicago v4.0 at our center (2021-2023). Demographics, organ involvement, pulmonary-function tests, echocardiography and reflux symptom scores (RDQ/GERDQ) were extracted from the hospital information system; age and sex matched non-SSc HRM subjects served as controls. Associations between Chicago categories and clinical variables were examined by multinomial logistic regression.</p><p><strong>Results: </strong>In our study, esophageal motility disorders were present in 76.7% of patients with systemic sclerosis, predominantly characterized by ineffective esophageal motility (IEM) (35%) and absent contractility (AC) (36.67%). The occurrence rate of AC rose with age. Symptoms of gastroesophageal reflux were more common in the AC group [Odds Ratio: 3.23 (1.02-10.22) vs 1.43(0.52-3.95), P<0.05, E value=2.99]. Diffusion capacity for carbon monoxide (DLCO) was significantly reduced in both IEM and AC (-2.03 vs -2.70, P value<0.05), with a more pronounced decrease in AC. Total lung capacity (TLC) and forced expiratory volume in one second (FEV1) exhibited stronger associations with AC (-1.04 and -0.8 respectively, p value<0.05). Upright HRM revealed more marked decreases in EGJ pressure and distal contractile integral (DCI) relative to the supine position in SSc patients, indicating that esophageal abnormalities may be more readily apparent during upright examination.</p><p><strong>Conclusions: </strong>Esophageal motility disorders in SSc were common and significantly associated with older age, gastroesophageal reflux symptoms, and reduced lung function. Future studies are needed to clarify whether early esophageal motility disorders are associated with disease progression and prognosis in patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1962332"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223886","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":"ZC3H15 in human tumors: a pan-cancer exploration of its clinical significance, molecular function, and association with the tumor immune microenvironment.","authors":"Bin Zhou, Jian Huang, Qifei Tao, Zhejin Sheng, Fabiao Zhang, Beige Jiang, Limei Li","doi":"10.3389/fimmu.2026.1901516","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1901516","url":null,"abstract":"<p><strong>Background: </strong>Zinc finger CCCH-type protein 15 (ZC3H15) is a ribosome-associated eukaryotic protein involved in many biological processes, including gene expression regulation, translation, and immune modulation. Although ZC3H15 has been implicated in the development of certain tumors, its expression, functional relevance, diagnostic potential, and prognostic value in a pan-cancer context remain not fully elucidated. This study conducts an integrative, systematic, and comparative analysis of ZC3H15 across 33 cancer types and subsequently provides further experimental validation in liver cancer.</p><p><strong>Methods: </strong>mRNA expression data of ZC3H15 were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Protein level validations were performed using the Human Protein Atlas (HPA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The cBioPortal database was used to analyze the genomic alteration of ZC3H15. Two pathway enrichment analysis methods were conducted to explore the biological functions and molecular mechanisms of ZC3H15 in pan-cancer.</p><p><strong>Results: </strong>The results indicated that ZC3H15 was overexpressed in a wide range of tumors. In certain cancers, particularly LIHC, LUAD, BRCA, LUSC, and HNSC, its expression was significantly correlated with poor patient prognosis. Mutations and amplifications were the most common gene alterations in ZC3H15. The GSCA database showed that methylation levels were reduced in most tumor types. Abnormal expression of ZC3H15 was related to immune cell infiltration. Gene enrichment analysis indicated that ZC3H15-related genes involved in tumor progression were significantly enriched in multiple cell cycle processes. We demonstrated that knockdown of ZC3H15 suppressed cell proliferation, migration, and invasion in two liver cancer cell lines, MHCC97H and Huh7, and two BRCA cell lines, MDA-MB-231 and Hs 578T. To further clarify the functional mechanism, subsequent immunofluorescence staining confirmed that ZC3H15 knockdown induced prometaphase arrest in MHCC97H and Huh7 liver cancer cells.</p><p><strong>Conclusions: </strong>Overall, this pan-cancer study demonstrates that ZC3H15 serves as a potential biomarker for cancer diagnosis, prognosis, and immune cell infiltration.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1901516"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224008","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":"Bioengineering strategies to enhance BCG immunotherapy against bladder cancer.","authors":"Senhao Li, Haige Chen, Bing Feng","doi":"10.3389/fimmu.2026.1888889","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1888889","url":null,"abstract":"<p><p>Bacillus Calmette-Guérin (BCG) remains the frontline immunotherapy for non-muscle-invasive bladder cancer (NMIBC), yet recurrence and non-response occur in over half of patients, highlighting the need for improved therapeutic strategies. Recent advances in bioengineering including genetic modification, synthetic biology, biomaterials, and delivery systems are expanding BCG from a traditional vaccine into a more versatile immunotherapeutic platform. In this review, we summarize the mechanisms of BCG-induced antitumor immunity and discuss current bioengineering strategies aimed at enhancing tumor interaction, innate immune activation, and modulation of the tumor immune microenvironment (TIME). We further highlight emerging approaches in delivery system design to improve intravesical retention and therapeutic efficacy. In addition, we discuss evolving perspectives on immune regulation in BCG therapy, including the potential contribution of type 2 immunity alongside canonical type 1 responses, as well as the role of trained immunity in sustaining antitumor effects. Finally, we outline key challenges for clinical translation and future directions toward more rational and precise BCG-based immunotherapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1888889"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223927","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}