Immunobiology最新文献

{"title":"Mannose receptor modulates hepatic stellate cell activation and alleviates liver fibrosis through immune-fibrotic crosstalk","authors":"Shiyue Tang,&nbsp;Shengnan Luo,&nbsp;Jun Zhang,&nbsp;Dehe Zhang,&nbsp;Xiaoping Wang,&nbsp;Haijun Chen","doi":"10.1016/j.imbio.2026.153189","DOIUrl":"10.1016/j.imbio.2026.153189","url":null,"abstract":"<div><h3>Background</h3><div>Liver fibrosis is characterized by excessive extracellular matrix (ECM) deposition and hepatocellular dysfunction. Activation of hepatic stellate cells (HSCs) is central to this process, yet the underlying regulatory mechanisms remain incompletely understood. The mannose receptor (MR), a pattern-recognition receptor involved in immune modulation and tissue remodeling, has been implicated in fibrotic diseases, but its role in hepatic fibrosis remains unclear.</div></div><div><h3>Methods</h3><div>A chronic liver fibrosis model was established in mice using repeated carbon tetrachloride (CCl₄) injection. Histology, serum biochemistry, quantitative PCR, and Western blotting were used to evaluate fibrosis, HSC activation, and MR expression. Correlations between MR and inflammatory cytokines were analyzed. In vitro, MR overexpression was used to assess its role in transforming growth factor-β (TGF-β)-induced HSC activation.</div></div><div><h3>Results</h3><div>CCl₄-induced fibrosis resulted in hepatocyte injury, ECM accumulation, and elevated ALT, AST, and triglyceride levels. HSC activation, indicated by increased α-SMA and collagen I expression, accompanied fibrosis progression. MR expression in liver tissue and soluble MR (sMR) levels in serum were significantly increased and were associated with inflammatory cytokines. In vitro, MR overexpression suppressed TGF-β–induced HSC activation without altering total Smad-3 expression.</div></div><div><h3>Conclusion</h3><div>These findings suggest that MR may play a regulatory role in hepatic fibrogenesis by modulating HSC activation and ECM deposition, potentially through interactions with the inflammatory microenvironment. Elevated MR and sMR levels may serve as candidate biomarkers for fibrosis progression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153189"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Shared pyroptosis pathways and crosstalk genes underpin inflammatory links between periodontitis and atherosclerosis” [Immunobiology 230 (2025) 152880]","authors":"Pinxin Zhan,&nbsp;Zhiying Feng,&nbsp;Xinqi Huang,&nbsp;Haoyang Xu,&nbsp;Shijun Xu,&nbsp;Shan Wang","doi":"10.1016/j.imbio.2026.153184","DOIUrl":"10.1016/j.imbio.2026.153184","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153184"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor H-related proteins as a protective evolutionary mechanism against microbial infections","authors":"Rosario García-Sánchez ,&nbsp;Alberto López-Lera ,&nbsp;Laura González-Sánchez ,&nbsp;Fernando Corvillo ,&nbsp;Agustín Tortajada ,&nbsp;Pilar Sánchez-Corral","doi":"10.1016/j.imbio.2026.153185","DOIUrl":"10.1016/j.imbio.2026.153185","url":null,"abstract":"<div><div>Factor H (FH) is the main regulator of the complement alternative pathway, and it is essential to prevent complement-mediated autologous damage. Many pathogens express FH-binding proteins on their surface that recruit human FH as a strategy to avoid or limit their elimination by the host complement. The FH-Related Proteins (FHR-1, FHR-2, FHR-3, FHR-4A, and FHR-5) share sequential and structural homology with FH that result from their common ancestry, but none of them can regulate complement like FH. While the precise contribution of FHRs in human complement is still not completely understood, it has been proposed that these proteins have been conserved along evolution because they outcompete FH binding to the microbial surfaces, thus allowing pathogen elimination. In this review, we recapitulate the current evidence of the interaction between FHRs and pathogens. We describe the results from “in vitro” studies with microbial isolates and purified proteins, and the few studies that have addressed the quantification of FH and FHRs in patients during infection. We also provide an analysis comparing the frequency of common genetic variants, including <em>ΔCFHR3-CFHR1,</em> in different geographical regions, and the incidence of Invasive Meningococcal Disease. All the data are discussed in the context of the role of FHRs as FH-deregulators, and at the light of recent findings supporting a function as complement activators.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153185"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement in tuberculosis infection and disease, a battle of two ancients","authors":"Karin Dijkman ,&nbsp;Simone A. Joosten ,&nbsp;Leendert A. Trouw","doi":"10.1016/j.imbio.2026.153183","DOIUrl":"10.1016/j.imbio.2026.153183","url":null,"abstract":"<div><div>Tuberculosis continues to kill over a million people every year, with an additional 10 million people falling ill. The ongoing efforts to eradicate the disease are hampered by an incomplete understanding of the mechanisms involved in the defense against tuberculosis. It has become clear that next to the well-known T-cell responses other components of the immune system also play important roles, both protective and detrimental, in the host defense against tuberculosis. In particular, the role of antibodies and complement are increasingly appreciated. However, the contribution of the complement system during <em>Mycobacterium tuberculosis</em> infection and disease remains poorly understood. The complement system is an intricate network of plasma proteins, which upon activation can achieve a powerful cytotoxic effect. Additionally, a range of antimicrobial and immune-modulating effector molecules, such as opsonins and chemoattractants, are generated. As a consequence, the role of the complement system in host defense extends beyond its cytotoxic effect, influencing both the innate and adaptive immune response. In this review, we discuss the many-faceted role of the complement system in tuberculosis, reviewing its involvement in infection, disease progression, and response to therapy, and provide a perspective on how the complement system can be harnessed to improve tuberculosis diagnostics, vaccines and therapeutics.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153183"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147798644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARID1A mutation is associated with an immunosuppressive microenvironment and poor prognosis in hepatocellular carcinoma: An integrated bioinformatics analysis","authors":"Manxian Huang ,&nbsp;Xiaobing Wan ,&nbsp;Hong Chen ,&nbsp;Juan Wu ,&nbsp;Min Liu ,&nbsp;Changli Sun","doi":"10.1016/j.imbio.2026.153190","DOIUrl":"10.1016/j.imbio.2026.153190","url":null,"abstract":"<div><h3>Background</h3><div>Identifying recurrent genetic mutations is crucial for advancing the understanding and treatment of hepatocellular carcinoma (HCC). The chromatin regulator ARID1A is frequently mutated in cancers, but its integrated impact on prognosis and the tumor immune microenvironment (TIME) in HCC is unclear.</div></div><div><h3>Methods</h3><div>Somatic mutation and transcriptome data from TCGA and ICGC databases were analyzed. Associations with tumor mutation burden (TMB) and prognosis were evaluated. Immune infiltration was estimated using CIBERSORT/ssGSEA. Pathway and immunomodulator analyses were performed. ARID1A expression was validated via tissue microarray and an independent cohort (GSE76427).</div></div><div><h3>Results</h3><div>Among 19 commonly mutated genes, <em>ARID1A</em> mutation was an independent prognostic factor for poorer overall survival and was associated with higher TMB. A nomogram integrating ARID1A status, TMB, and stage showed good predictive accuracy. ARID1A mRNA/protein was upregulated in HCC tissues, correlating with advanced stage. ARID1A-mutant tumors exhibited distinct pathway enrichments (e.g., p53 signaling, drug metabolism). The ARID1A-mutant TIME was characterized by an increased proportion of naive CD4⁺ T cells and significantly elevated expression of specific immunomodulators, including the immunosuppressive molecules IDO1 and BTLA. Correlation analysis further linked this molecular signature to the specific immune cell landscape, suggesting an “inflamed but suppressed” TME.</div></div><div><h3>Conclusions</h3><div>ARID1A mutation defines an aggressive HCC subtype characterized by high TMB coupled with a distinct immunosuppressive TIME. These findings suggest ARID1A status has prognostic value and may inform combination immunotherapy strategies, such as targeting IDO1 or BTLA, warranting further clinical and mechanistic validation.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153190"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of anti-DFS70 positivity with disease activity in systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis: a cross sectional study","authors":"Esra Dilsat Imrak ,&nbsp;Alev Cetin Duran","doi":"10.1016/j.imbio.2026.153193","DOIUrl":"10.1016/j.imbio.2026.153193","url":null,"abstract":"<div><h3>Objective</h3><div>Anti-DFS70 antibodies have been proposed as a potential marker of lower disease activity in systemic autoimmune diseases, but evidence remains conflicting. This study aimed to investigate the association between anti-DFS70 positivity and disease activity in three systemic autoimmune diseases: systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), and systemic sclerosis (SSc).</div></div><div><h3>Methods</h3><div>This cross-sectional study included 246 patients (59 SLE, 102 pSS, 85 SSc). Anti-DFS70 positivity was determined by immunoblot method. Disease activity was assessed using SLEDAI-2 K (SLE), ESSDAI (pSS), and EUSTAR activity index (SSc). Multivariate linear regression models were constructed for each disease cohort, adjusting for age, sex, disease-specific autoantibodies, glucocorticoid use, and interstitial lung disease (for SSc).</div></div><div><h3>Results</h3><div>Anti-DFS70 positivity was observed in 14 (23.3%) SLE, 23 (22.5%) pSS, and 12 (14.1%) SSc patients. In univariate analyses, anti-DFS70-positive SLE patients had significantly lower SLEDAI-2 K scores (median 3 vs 4, <em>p</em> = 0.001), lower anti-dsDNA positivity (6.7% vs 40.0%, <em>p</em> = 0.014), and less frequent glucocorticoid use (13.3% vs 46.6%, <em>p</em> = 0.02). However, in multivariate regression models, anti-DFS70 positivity was not independently associated with disease activity in any of the three diseases (SLE: β = −1.197, <em>p</em> = 0.191; pSS: β = −0.181, <em>p</em> = 0.394; SSc: β = −0.578, <em>p</em> = 0.187). Correlation analysis revealed a significant negative correlation between anti-DFS70 titre and SLEDAI-2 K in SLE (ρ = −0.440, q &lt; 0.001), which was lost after multivariate adjustment, confounded by anti-dsDNA positivity and glucocorticoid use.</div></div><div><h3>Conclusion</h3><div>No independent association was demonstrated with Anti-DFS70 positivity and low disease activity in SLE, Sjögren's syndrome, or systemic sclerosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153193"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147995489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlighting the changes of the Lymphocyte-to-Monocyte ratio in B-cell non-Hodgkin Lymphoma with the treatment and its association with the FLT3/FLT3LG system","authors":"C.K. Nandasena ,&nbsp;P.W.D.C.C. Jayathilake ,&nbsp;H.A.S.G. Dharmarathne ,&nbsp;P. Kaluarachchi ,&nbsp;S. Suresh ,&nbsp;A.D. De Silva ,&nbsp;I.C. Perera ,&nbsp;D.U. Kottahachchi","doi":"10.1016/j.imbio.2026.153194","DOIUrl":"10.1016/j.imbio.2026.153194","url":null,"abstract":"<div><h3>Background</h3><div>B-cell Non-Hodgkin Lymphoma (B-NHL) is a group of lymphoid malignancies characterized by dysregulation of lymphocytes and monocytes. CD135/FLT3 (FMS-like tyrosine kinase 3) and its ligand (FLT3LG) play crucial roles in white blood cell (WBC) proliferation, and their ratios are meaningful indicators of treatment response.</div></div><div><h3>Methods</h3><div>The study involved three groups: pre-treatment BNHL (<em>n</em> <em>=</em> <em>50</em>), post-treatment BNHL (<em>n</em> <em>=</em> <em>50</em>), and Healthy controls (<em>n</em> <em>=</em> <em>50</em>). Peripheral blood specimens were analyzed to detect FLT3/CD135 expression using flow cytometry, plasma-FLT3LG by ELISA, and WBC ratios.</div></div><div><h3>Results</h3><div>Post-treatment and Healthy groups showed FLT3^Low expression, whereas 22% of the Pre-treatment group showed FLT3^High expression in a subset of 11b+ cells in the monocytic region. Therefore, the pre-treatment-BNHL was divided into Pre-FLT3^High and Pre-FLT3^Low groups for comparison. Significantly higher (<em>p</em> &lt; 0.05) Neutrophil-to-Lymphocyte (NLR): 24.25 ± 22.39, Neutrophil-to-Monocyte (NMR): 25.12 ± 21.22, and Platelet-to-Lymphocyte (PLR): 875.93 ± 1261.49, and significantly lower (<em>p</em> &lt; 0.05) Lymphocyte-to-Monocyte (LMR): 2.37 ± 2.74, Mean plasma-FLT3LG (25.26 ± 15.35 pg/mL), and a negative correlation between FLT3LG and PLR by Spearman analysis were observed as key differences in the Pre-FLT3^High group than others. ROC analysis showed higher AUCs: 0.810 for NLR, 0.733 for LMR, and 0.713 for PLR, discriminating the whole Pre-treatment-BNHL population from healthy controls. Accordingly, the overall model quality values for NLR (0.721) and LMR (0.690) were the best predictors for differentiating Pre-treatment-BNHL from Healthy.</div></div><div><h3>Conclusion</h3><div>NLR and LMR were good predictors for distinguishing Pre-treatment-BNHL from Healthy. The Pre-FLT3^High group showed more pronounced deviations in WBC ratios and FLT3LG levels than the other groups. Further studies are warranted to explore the clinical effect of FLT3^High 11b + monocytic cells in B-NHL.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153194"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The alterations of blood immune subpopulations, cytokines, and metabolites in anti-acetylcholine receptor antibody-positive myasthenia gravis: a real-world, observational, high-throughput study","authors":"Huanyu Meng ,&nbsp;Xiaoyu Chen ,&nbsp;Zhuoying Zhu ,&nbsp;Guangqiang Sun ,&nbsp;Lu He ,&nbsp;Qinming Zhou ,&nbsp;Liang Li ,&nbsp;Xinying Yang ,&nbsp;Xingkun Chu ,&nbsp;Dabing Yang ,&nbsp;Yuan Feng ,&nbsp;Jing Zhang ,&nbsp;Sheng Chen","doi":"10.1016/j.imbio.2026.153192","DOIUrl":"10.1016/j.imbio.2026.153192","url":null,"abstract":"<div><div>Comprehensive profiling of peripheral blood may reveal candidate markers and therapeutic targets for anti-AChR antibody positive myasthenia gravis (MG) patients. We enrolled 37 anti-AChR antibody positive MG patients and 37 healthy controls (HCs), and blood immune cells were analyzed by mass cytometry, plasma proteins were determined by Cytokine Array, and metabolites were measured by targeted metabolomics. Compared with HCs, anti-AChR antibody positive MG patients showed increased classical monocytes and Th2-like cells, and decreased Th1-like cells, regulatory T cells, CD4⁺T, and CD28⁺T cells. Cytokine profiling revealed reduced retinol-binding protein 4 (RBP4), epithelial neutrophil-activating peptide 78 (ENA-78), and stem cell factor receptor (SCF-R), but elevated angiogenin, RANTES (CCL5), and cystatin-A. Metabolomics indicated lower dehydroepiandrosterone sulfate (DHEAS), cystine, and arginine, with higher lactate, sarcosine, and ornithine. Notably, glucocorticoid pretreatment reduced myeloid dendritic cells, Th2-like cells, dendritic cells, classical monocytes, and total monocytes. Integrated multi-omics analysis identified immune–metabolic interactions associated with anti-AChR antibody positive MG pathogenesis. This study highlights potential candidate markers and provides insights for targeted therapy.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153192"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blue light-emitting diode phototherapy reduces cerebral parasitic load and inflammation in murine congenital toxoplasmosis model","authors":"Débora Nonato Miranda Toledo ,&nbsp;Natiele Carlos ,&nbsp;Giulia Caroline Dantas-Vieira ,&nbsp;Marina Monteiro de Castro Burle ,&nbsp;Lauro de Assis Duarte-Junior ,&nbsp;Maria Laura Cruz Castro ,&nbsp;Talita Rodrigues dos Santos ,&nbsp;Guilherme Paula Costa ,&nbsp;Cristiano Schetini de Azevedo ,&nbsp;Daniela Caldeira Costa ,&nbsp;Élida Mara Leite Rabelo ,&nbsp;Rodrigo Fernando Bianchi ,&nbsp;Érica Santos Martins-Duarte ,&nbsp;André Talvani","doi":"10.1016/j.imbio.2026.153182","DOIUrl":"10.1016/j.imbio.2026.153182","url":null,"abstract":"<div><div>The search for effective therapies to eradicate <em>Toxoplasma gondii</em>, the causative agent of toxoplasmosis, has spanned decades with limited success. Current drugs, including sulfadiazine, spiramycin, and pyrimethamine, face limitations such as parasite resistance, high cellular toxicity, inconsistent efficacy in the acute phase of disease, and the lack of effect in the chronic phase. This study evaluates an innovative adjunctive approach using light-emitting diode phototherapy (BLP) to control <em>T. gondii</em> acute infection during pregnancy. For that, pregnant female Swiss mice (8–9 weeks) were orally infected with 10 cysts of the ME49 strain of <em>T. gondii</em> and exposed to BLP (460 nm, 7 μW/cm2) or conventional white light for 12 h/day over 12 days. After the treatment period, the females were euthanized, and the fetuses, placentas, liver, spleen, maternal brain, and blood were collected for analysis. BLP reduced parasitic load in brain tissue and modulated tissue-specific immune responses, with increased IL-10 in the brain and fetal tissues, elevated CCL2 in liver parenchyma and fetal tissues, and induction of TNF in fetal samples. Serum ferritin and oxidative stress, thiobarbituric acid-reactive substances (TBARS), and superoxide dismutase (SOD) increased in infected mice exposed to BLP, while catalase (CAT) remained unchanged. These findings suggest that BLP exerts both immunomodulatory effects on the infected host and cytotoxicity against <em>T. gondii</em>, supporting its potential as an adjunctive approach for etiological treatment in congenital toxoplasmosis.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153182"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated single-cell and bulk RNA-seq analysis identifies BCAA metabolism-related prognostic signatures in head and neck squamous cell carcinoma","authors":"Dandan Lu ,&nbsp;Yongjun Liang ,&nbsp;Tao Mo ,&nbsp;Abdeyrim Arikin","doi":"10.1016/j.imbio.2026.153200","DOIUrl":"10.1016/j.imbio.2026.153200","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Impaired metabolism of branched-chain amino acids (BCAAs) has been linked to cancer progression; however, the specific mechanisms underlying BCAA metabolism in head and neck squamous cell carcinoma (HNSCC) remain unclear. This study aimed to identify prognostic genes associated with BCAA metabolism in HNSCC and elucidate their functional roles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;HNSCC-related datasets (TCGA-HNSCC, GSE65858, GSE41613, GSE103322, and GSE140042) were analyzed, and candidate genes were identified by intersecting differentially expressed genes from differential expression analysis with key module genes associated with BCAA metabolism–related gene (BCAA-MRG) scores from weighted gene coexpression network analysis. Prognostic genes were subsequently selected to construct a risk model using univariate Cox regression analysis, proportional hazards testing, and least absolute shrinkage and selection operator regression. Independent prognostic analysis, enrichment analysis, and immune microenvironment assessment were subsequently performed. Moreover, single-cell RNA sequencing (scRNA-seq) and pseudotime analysis were used to evaluate prognostic gene expression at the cellular level. RT-qPCR was used to validate gene expression levels in HNSCC tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;PRDX6&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, and &lt;em&gt;ADA&lt;/em&gt; were identified as prognostic genes for the risk model. The HNSCC samples were stratified into a high-risk group (HRG) and a low-risk group (LRG), with LRG showing notably better survival outcomes. A nomogram model based on risk score and age demonstrated excellent predictive performance for patients with HNSCC. Furthermore, enrichment analysis revealed that the pentose phosphate pathway and fructose and mannose metabolism were substantially associated with HNSCC progression. Differences in the infiltration levels of 20 immune cell types (including plasmacytoid dendritic cells, mast cells, and T follicle helper cells) and the expression of 10 immune checkpoints (such as CD276, CD27, and CD40) were observed between HRG and LRG. Epithelial cells, which exhibited higher expression of prognostic genes, were highlighted as key cells. Notably, the expression trends of these genes varied across different cell differentiation stages. RT-qPCR validation revealed that &lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, and &lt;em&gt;ADA&lt;/em&gt; were highly expressed in the tumor group, whereas &lt;em&gt;PRDX6&lt;/em&gt; showed no significant difference between the tumor and normal tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;A four-gene BCAA metabolism–related signature (&lt;em&gt;SMS&lt;/em&gt;, &lt;em&gt;PRDX6&lt;/em&gt;, &lt;em&gt;GSTO1&lt;/em&gt;, &lt;em&gt;ADA&lt;/em&gt;) was identified that stratifies patients with HNSCC into distinct risk groups with different survival and immune microenvironments. The model suggests BCAA–immune interactions, specifically in epithelial cells, provide preliminary insights for prognosis and therapy. Nevertheless, these co","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"231 3","pages":"Article 153200"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}