Frontiers in Immunology最新文献

{"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":"Primary ocular adnexal MALT lymphoma involving the upper eyelid in a young woman: a case report and literature review.","authors":"Qiming Zhang, Liying Gu, Jing Yuan, Rui Wang, Yujuan Xu, Qiong Liu, Hongbo Li, Kefeng Shen, Ting Chen","doi":"10.3389/fimmu.2026.1920364","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1920364","url":null,"abstract":"<p><p>Primary ocular adnexal MALT lymphoma (POAML) is a rare indolent small B-cell lymphoma that primarily involves the orbit, conjunctiva, and lacrimal gland, with a high risk of early misdiagnosis. Herein, we report a rare case of POAML arising in the right upper eyelid of a 35-year-old woman, who presented with progressive eyelid swelling. The diagnosis was established by surgical excision, histopathological examination, and immunoglobulin gene rearrangement analysis. No systemic involvement was identified, and the disease was staged as Ann Arbor IE. The patient received local radiotherapy (28 Gy) and achieved complete remission, remaining disease-free during a 3.5-year follow-up. Literature review indicates that POAML predominantly affects middle-aged and elderly individuals, although younger age and female predominance have been reported in Asian populations. Clinical manifestations vary by site and include orbital mass, proptosis, globe displacement, and ocular motility restriction. Conjunctival lesions typically present as hyperemia, chemosis, or a characteristic \"salmon-pink\" appearance. Histologically, POAML is characterized by diffuse proliferation of centrocyte-like cells, follicular colonization, and lymphoepithelial lesions (LELs), with CD20 and CD79a positivity. Previous studies have identified recurrent molecular alterations in POAML, including changes affecting the BCR/NF-κB, epigenetic, and NOTCH signaling pathways; rearrangements of <i>MALT1</i>, <i>BIRC3</i>, <i>BCL10</i>, and <i>FOXP1</i>; and chromosomal abnormalities such as trisomy 3 and trisomy 18. Chronic antigenic stimulation associated with infection or autoimmune disease is considered a major predisposing factor. Treatment is stage-dependent, with surgery, radiotherapy, or observation for early-stage disease and immunochemotherapy for advanced disease. This case underscores that POAML should be considered in the differential diagnosis of progressive eyelid swelling, even in young women, as timely and accurate diagnosis and appropriate treatment can lead to a favorable prognosis.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1920364"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223847","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":"Biofilm-host immunometabolic crosstalk in <i>Staphylococcus aureus</i> orthopedic implant infection: mechanisms and translational constraints.","authors":"Jixin Chen, Qinxin Zhou, Dongdong Cao, Weijie Yu, Yongming Zhang, Jianliang Chen, Xiaodong Zheng, Feng Ye","doi":"10.3389/fimmu.2026.1957346","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1957346","url":null,"abstract":"<p><p>Orthopedic implant biofilms are not only antibiotic-tolerant bacterial communities but metabolically active niches that reshape host immunity. Compared with planktonic infection, mature biofilms impose spatial and metabolic constraints that can uncouple leukocyte recruitment from sterilizing activity. Neutrophils can penetrate and phagocytose portions of Staphylococcus aureus biofilms, but clearance becomes incomplete as biofilms mature and may coexist with degranulation and neutrophil extracellular trap-associated tissue injury. Macrophages show impaired access and bactericidal programming, and biofilm-derived lactate can promote interleukin-10 (IL-10) through histone deacetylase 11 (HDAC11)/HDAC6-dependent epigenetic reprogramming in experimental systems. Human periprosthetic joint infection (PJI) tissues are enriched in granulocytic myeloid-derived suppressor cells (G-MDSCs), whereas the glycolysis/hypoxia-inducible factor 1-alpha (HIF-1alpha) phenotype and its contribution to persistence are supported primarily by murine PJI, with limited human transcriptomic corroboration. In chronic S. aureus infection models, MDSC-derived lactate can suppress CD4-positive (CD4+) T-cell glycolysis; conversely, immune pressure drives heterogeneous bacterial metabolic, stress-response, and virulence programs. We synthesize these interactions as bidirectional biofilm-host immunometabolic crosstalk linking persistent infection to bone-interface damage. Source control and antibiotics remain essential. Local, time-limited, dysfunction-directed host interventions are presented here as a hypothesis-generating translational framework rather than evidence-based clinical recommendations, because host-directed immunometabolic therapies for PJI remain preclinical.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1957346"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223858","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":"Beyond combination: sequencing priming modalities before immune checkpoint inhibitors to convert immunologically cold tumors toward an ICI-responsive phenotype.","authors":"Weiqiang Fan, Hui Xu, Yating Wu, Yonghai Peng","doi":"10.3389/fimmu.2026.1947737","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1947737","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have transformed oncology but largely spare immunologically \"cold\" tumors, those with sparse T-cell infiltration, low PD-L1 expression, and an immunosuppressive microenvironment. The prevailing response has been a combination: adding a priming modality to a checkpoint inhibitor, most often concurrently. We argue that this \"addition\" paradigm has plateaued in cold disease because it treats combination as arithmetic rather than as a temporally ordered program, and that timing, the order and interval of interventions, may govern outcome as much as the choice of agents. We first define what makes a tumor immunologically cold and why simultaneous stacking reaches a ceiling. We then assemble the clinical evidence that timing already shapes outcomes: most maturely in the scheduling of radiotherapy relative to checkpoint blockade and, strikingly, in neoadjuvant-versus-adjuvant immunotherapy, where the same agent changes outcome according to when it is given. We synthesize the temporal immunobiology that makes ordering matter-antigen release and dendritic-cell priming kinetics, the vascular-normalization window, compensatory adaptive-resistance windows, and the slow dynamics of the gut microbiome-and review, mechanism by mechanism, the timing evidence for microenvironment priming, checkpoint inhibition, and microbiome modulation, emphasizing that mistiming can be harmful rather than merely ineffective. We describe how several groups are translating this principle into integrated, time-sequenced strategies and set out, as one concrete and falsifiable instantiation, a three-axis schema, which we term TMEp-CI-M, illustrated by cross-tumor proof-of-concept experience and framed as hypothesis-generating rather than validated. A therapy built on timing will require dynamic biomarkers of window state and adaptive, biomarker-driven trials. For cold tumors, re-sequencing the agents we already have, rather than adding new ones, may be among the highest-yield and lowest-cost hypotheses in immuno-oncology and one that can be tested now.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1947737"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223915","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":"Early recognition of eosinophilic granulomatosis with polyangiitis in outpatient settings: musculoskeletal and gastrointestinal clues beyond respiratory disease.","authors":"Ernesto Aitella, Massimo De Martinis, Lia Ginaldi","doi":"10.3389/fimmu.2026.1964154","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1964154","url":null,"abstract":"<p><p>Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem immune-mediated disease characterized by adult-onset asthma, eosinophilic inflammation, and necrotizing vasculitis of small-to-medium-sized vessels. Diagnosis is frequently prompted by clinically overt neurological, cardiac, renal, cutaneous, or gastrointestinal involvement. However, potentially informative manifestations may already be recognizable earlier, particularly when asthma, chronic rhinosinusitis with nasal polyps, and blood eosinophilia coexist with otherwise nonspecific extrapulmonary findings. Most cohorts describe manifestations at diagnosis or during established disease and provide limited information on their early temporal appearance across different specialties. This gap is particularly relevant to arthralgia and myalgia, which are common but poorly characterized, and to eosinophilic gastrointestinal manifestations that may initially be classified as organ-restricted eosinophilic gastrointestinal disorders. Biopsy-proven myositis is rare but has occasionally been reported at presentation or before clinically recognizable neuropathy. This review examines early and potentially recognizable manifestations of EGPA across outpatient settings, with particular attention to musculoskeletal symptoms, objective muscle involvement, eosinophilic gastrointestinal disease, and the therapeutic implications of distinguishing organ-restricted eosinophilic disease from systemic EGPA.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1964154"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223916","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":"Vedolizumab treatment in adults with immunodeficiency-associated enteropathy: a case series.","authors":"Ernestina Angarola, María Josefina Etchevers, Juan Andres De Paula, Maria Florencia Sanchez, Juan Pablo Santino, Diana Liberatore","doi":"10.3389/fimmu.2026.1953966","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1953966","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory gastrointestinal disease is a common manifestation of inborn errors of immunity (IEI) and may affect any segment of the gastrointestinal tract. Vedolizumab, a gut-selective anti-integrin approved for inflammatory bowel disease, has been scarcely studied in IEI. We describe our experience with vedolizumab in adults with immunodeficiency-associated enteropathy.</p><p><strong>Methods: </strong>We conducted a retrospective case series of adults with humoral or combined immunodeficiency and inflammatory gastrointestinal disease treated with vedolizumab at a single tertiary referral center. Clinical, endoscopic, laboratory and histopathological responses were assessed.</p><p><strong>Results: </strong>Four adult patients with immunodeficiency-associated enteropathy received vedolizumab. Two patients achieved sustained clinical and endoscopic/histological remission, both of whom had predominant villous atrophy (one with TRAF3 haploinsufficiency, and the other had multiple autoimmune manifestations, refractory immune thrombocytopenia and agammaglobulinemia following rituximab). Another patient with combined immunodeficiency and protein-losing enteropathy had marked clinical improvement with mild histologic response, but relapsed at two years in the setting of norovirus and Clostridium difficile infection. In contrast, a woman with common variable immunodeficiency, autoimmune hepatitis, and severe refractory pancolitis failed to respond to vedolizumab and subsequently developed CMV superinfection, requiring treatment escalation.</p><p><strong>Conclusions: </strong>In this case series, vedolizumab was associated with clinical improvement predominantly in patients with villous atrophy rather than refractory colitis. These findings are hypothesis-generating and support further evaluation of vedolizumab as a therapeutic option for selected patients with immunodeficiency-associated enteropathy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1953966"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223929","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":"Effect of immunosuppressive drugs on glucose-stimulated insulin secretion: concentration-response studies in dynamic perifusion assays.","authors":"Sung-Ting Chuang, Brandon Watts, Oscar Alcazar, Peter Buchwald","doi":"10.3389/fimmu.2026.1947013","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1947013","url":null,"abstract":"<p><p>Immunosuppressive drugs, which are required to maintain graft function in transplant recipients, are associated with many unavoidable side effects including posttransplant diabetes mellitus (PTDM) that involves both peripheral insulin resistance and impairment of insulin secretion. To characterize in detail the concentration-dependency of the effect of well-known immunosuppressive drugs on glucose-stimulated insulin secretion (GSIS), we performed dynamic perifusion studies with human pancreatic islets. The effect on the time-profile of GSIS has been assessed over a wide concentration range for several clinically relevant immunomodulatory therapies, including small-molecule drugs (cyclosporine, sirolimus, tacrolimus, prednisolone acetate, and loteprednol etabonate) and biologics (abatacept and anti-CD40L), plus a prospective β-cell proliferation-inducing agent (harmine). While biologics showed no significant detrimental effects after one-day treatment even at relatively high concentrations (5 µM), all small-molecule drugs inhibited insulin secretion in a concentration-dependent manner, although glucocorticoids showed a distinct response pattern. Calcineurin and mTOR inhibitors preserved GSIS within their therapeutic ranges but progressively distorted its time-profile at higher concentrations and completely suppressed secretion at the highest levels, where they were also cytotoxic. Cyclosporine exhibited the least, only about 35-fold, separation between its therapeutic target (<i>C</i> _targ) and half-maximal GSIS inhibitory (IC₅₀) concentrations. Glucocorticoids did not alter the shape of the time-profile but inhibited overall insulin secretion even at therapeutic levels without affecting islet viability. Their inhibitory effect only increased slowly with concentration and did not follow a classic sigmoid pattern that has unity Hill slope. These findings establish quantitative benchmarks for immunosuppressant-induced β-cell toxicity and provide a framework for optimizing immunosuppressive regimens to reduce the risk of PTDM.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1947013"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223943","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":"Histidine alleviates copper-induced intestinal inflammation through oxidative stress-mediated mitochondrial damage and the Hif1α-Tnfα/Il1β pathway.","authors":"Chongchao Zhong, Fang Chen, Shaoxia Lu, Shicheng Han, Hongbai Liu, Chang'an Wang","doi":"10.3389/fimmu.2026.1960076","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1960076","url":null,"abstract":"<p><strong>Introduction: </strong>Copper (Cu) is an essential trace element for vertebrates, but excessive intake can induce intestinal toxicity. Whether nutritional intervention can alleviate Cu overload-induced intestinal damage and the underlying mechanisms remain unclear. In this study, we combined <i>in vivo</i> animal experiments with <i>in vitro</i> cell models to investigate the protective effect of histidine against Cu-induced intestinal inflammation and its molecular mechanisms.</p><p><strong>Methods: </strong>Rainbow trout (weight: 7.24 ± 0.03 g) were fed diets containing 3.11 mg Cu/kg and 6.89 g His/kg (Control), 12.69 mg Cu/kg and 6.71 g His/kg (Cu), 3.24 mg Cu/kg and 10.94 g His/kg (His), 12.37 mg Cu/kg and 10.87 g His/kg (Cu+His) for 8 weeks. Intestinal epithelial cells (IECs) were isolated from rainbow trout and incubated for 24-h in Cu (10 μM) and His (2.5 mM) solution. Histopathology, ultrastructural structure, oxidative stress, mitochondrial damage, and inflammation were determined in the intestine and IECs; fluorescence staining (DCFH-DA and JC-1), immunoblotting, immunofluorescence, siRNA, and ChIP were performed on IECs.</p><p><strong>Results: </strong>Our research results indicate that Cu can induce intestinal oxidative stress, which in turn leads to mitochondrial dysfunction and activation of the Hif1α-Tnfα/Il1β signaling axis, ultimately exacerbating intestinal inflammatory responses. In contrast, co-treatment with Cu and histidine markedly attenuated the intestinal inflammatory phenotype. Mechanistically, histidine exerts anti-inflammatory effects by inhibiting oxidative stress, improving mitochondrial function and suppressing Hif1α, thereby preventing the occurrence of intestinal inflammation.</p><p><strong>Discussion: </strong>This study is the first to elucidate the mechanism by which histidine alleviates Cu-induced intestinal inflammation and delineated the critical regulatory role of mitochondrial damage and the Hif1α-Tnfα/Il1β pathway in this process within a fish model. It provides a new theoretical basis for mitigating heavy metal toxicity through nutritional intervention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1960076"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224027","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":"Integrative multi-omics analysis reveals a membrane tension signature associated with tumor-stroma crosstalk in hepatocellular carcinoma.","authors":"Pengfei Zhu, Pengcheng Zhu, Zijuan Zhu, Gaozhong Bian, Yungang Liu, Qifan Yang, Peipei Luo","doi":"10.3389/fimmu.2026.1978174","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1978174","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated membrane tension (MT) drives tumor cell migration, invasion, and immune evasion, yet the prognostic value of MT-related genes (MTRGs) in hepatocellular carcinoma (HCC) remains unclear.</p><p><strong>Methods: </strong>We integrated transcriptomic and clinical data from TCGA, ICGC, and GEO. A three-gene MTRG prognostic signature was developed through univariate and LASSO-Cox regression, and validated using Kaplan-Meier analysis, time-dependent ROC curves, and calibration plots. Functional enrichment, immune infiltration, tumor mutational burden, and immunotherapy response was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Single-cell and spatial transcriptomics were used to investigate the mechanistic role of CFL1 in tumor-stroma crosstalk.</p><p><strong>Results: </strong>The signature (CFL1, CRTC2, SRGAP2) stratified HCC patients into high- and low-risk groups with distinct overall survival (OS). High-risk tumors showed coordinated activation of MT and ECM-remodeling pathways alongside an immunosuppressive microenvironment. In silico analyses suggested that CFL1-high tumor cells may transmit MDK signals to fibroblasts (via SDC2, NCL, and ITGA4-ITGB1) and to T cells (via NCL). Spatial transcriptomics confirmed predominant CFL1 enrichment in stromal compartments. The signature was an independent prognostic factor, and the nomogram showed promising clinical utility.</p><p><strong>Conclusions: </strong>This three-gene MTRG-associated signature is associated with predicted immunotherapy response based on computational analysis in HCC. Our results suggest a potential link between biophysical MT and tumor stroma co evolution and represent a potential therapeutic direction warranting further experimental validation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1978174"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223746","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 blood-brain tumor barrier as a spatial immune checkpoint in glioblastoma: leukocyte entry, perivascular retention, and therapeutic implications.","authors":"Fangbo Lin","doi":"10.3389/fimmu.2026.1957858","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1957858","url":null,"abstract":"<p><p>Glioblastoma (GBM) combines heterogeneous vascular dysfunction with a predominantly myeloid immune landscape. This Mini Review focuses on a specific problem: vascular permeability is not equivalent to productive leukocyte access. Entry requires endothelial capture, chemokine-guided arrest, transendothelial migration, release from perivascular sites, intratumoral dispersion, target recognition, and sustained effector function. Human tissue and spatial studies show regionally distinct neurovascular and myeloid states, whereas much of the causal evidence for trafficking and retention remains preclinical. We therefore distinguish published observations from a hypothesis-generating model in which the blood-brain tumor barrier (BBTB) and perivascular myeloid niche can act as coupled but separable checkpoints. The main conceptual advance is not the already recognized heterogeneity of the BBTB, but the argument that leakage-based imaging should not be used as a surrogate for immune-cell entry and that each trafficking stage requires its own pharmacodynamic readout. We summarize regional BBTB states, differential lymphoid and myeloid access, and selected strategies-vascular normalization, myeloid reprogramming, local cell delivery, and focused ultrasound-while emphasizing their evidence limits. Clinical translation will require spatially registered human sampling, explicit model provenance, and tests that can reject individual components of the framework.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1957858"},"PeriodicalIF":7.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223872","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}