Cytokine最新文献

{"title":"Dynamic changes in the frequency of classical CD14HighCD16- and inflammatory CD14++CD16+ monocyte subsets in patients with advanced liver fibrosis","authors":"Pedro V. da Silva-Neto ,&nbsp;Grenda L. Pereira ,&nbsp;Priscila S. Souza ,&nbsp;Diana M. Toro ,&nbsp;Wivian da C.C. Silva ,&nbsp;Geyse A.S. Soares ,&nbsp;Walter L. Lima-Neves ,&nbsp;Juliana S. Affonso ,&nbsp;Keyla S. Sousa ,&nbsp;Jéssica A. Silva ,&nbsp;Allyson G. Costa ,&nbsp;Flamir S. Victoria ,&nbsp;Marilu Barbieri-Victoria ,&nbsp;Andréa M. Tarragô ,&nbsp;Adriana Malheiro","doi":"10.1016/j.cyto.2025.157088","DOIUrl":"10.1016/j.cyto.2025.157088","url":null,"abstract":"<div><div>Hepatitis C is a global health problem, with approximately 71 million individuals chronically infected worldwide. During chronic inflammatory processes, the elevated expression of inflammatory mediators appears to influence the phenotype of circulating monocytes. Our objective was to investigate changes in the phenotypes of peripheral monocyte subsets and the profile of circulating mediators in patients from the Brazilian Amazon during chronic hepatitis C and associated with different degrees of liver fibrosis.</div></div><div><h3>Material and methods</h3><div>This is an observational study involving 30 individuals treated with DAAs and 15 healthy controls, tested for liver function, fibrosis scores (AST/platelet ratio index, FIB-4), percentage of peripheral blood monocyte subsets assessed with based on CD14/CD16 expression. The analysis of soluble immunological biomarkers was performed using the flow cytometry methodology.</div></div><div><h3>Results</h3><div>Chronic HCV patients showed decreased platelet counts and increased viral load, ALT, AST, alkaline phosphatase in individuals with high fibrosis scores (FIB-4 ≥ F2). Data analysis demonstrated a lower frequency of CD14^HighCD16⁻HLA-DR⁺ cells, while inflammatory CD14⁺⁺CD16⁺HLA-DR⁺ monocytes increased the expression of CD11a and CD11b integrins, CD49d activation markers, and the inflammatory receptor P2X7. Serum cytokine expression showed that liver fibrosis is associated with higher serum levels of IL-6, CXCL8, and CXCL9 compared to mild liver disease.</div></div><div><h3>Conclusions</h3><div>In conclusion, our findings demonstrated that Chronic HCV infection alters the frequency of peripheral inflammatory monocyte subsets, impacting cellular markers and activation in severe liver impairment (FIB-4 ≥ F2). Soluble biomarkers modulate pro-inflammatory monocyte phenotypes, linked to inflammation and fibrosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157088"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterising interleukin-27 (IL-27) responses in human blood derived macrophage cells","authors":"Thomas Helps ,&nbsp;Christa Baker ,&nbsp;Heather M. Wilson ,&nbsp;Simon Arthur ,&nbsp;Graeme I Murray ,&nbsp;Mairi H. McLean","doi":"10.1016/j.cyto.2025.157097","DOIUrl":"10.1016/j.cyto.2025.157097","url":null,"abstract":"<div><div>Macrophages are key cells in the pathogenesis of chronic inflammatory diseases. Interleukin (IL)-27 is a pleiotropic cytokine with mostly immunoregulatory functions and associated with a wide array of diseases. There is little knowledge on the effects of IL-27 on human macrophages. Here, we characterise the effect of IL-27 on human blood derived CD14+ monocyte derived macrophages (MDMs), in resting state and under inflammatory stimulation (+LPS/PepG), through targeted transcriptomic expression profile, phagocytosis of <em>E. coli</em> bioparticles and expression of intracellular and secreted proteins by DIA mass spectrometry and multiplex ELISA, respectively. There was no change in pro-inflammatory cytokine gene expression with IL-27. IL-27 led to changes in the chemokine secretome, inducing a significant upregulation of the chemokines CXCL9 and CXCL10 and reduced expression of CCL2, CCL7, CCL13, CCL18, CCL24, CXCL13, IL-10 and Midkine. Macrophage phagocytosis was not affected by IL-27. IL-27 effects on intracellular proteome were subtle overall. Using unadjusted <em>p</em> values, changes were most pronounced in the resting state, with a significant (<em>p</em> &lt; 0.05) increase in 106 and decrease in 11 proteins. Enrichment analysis suggested regulation of several biological processes by IL-27, including cellular response to type II interferon. Overall, we demonstrate novel biology of IL-27 mediated effects in human macrophages.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157097"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between plasma ANGPTL4 levels and the risk of 24 cancers: a prospective cohort study","authors":"Xi Cheng ,&nbsp;Shuzhen Zhao ,&nbsp;Mingyi Du ,&nbsp;Chengnan Guo ,&nbsp;Xingdong Chen ,&nbsp;Tiejun Zhang ,&nbsp;Zhenqiu Liu","doi":"10.1016/j.cyto.2025.157089","DOIUrl":"10.1016/j.cyto.2025.157089","url":null,"abstract":"<div><h3>Background</h3><div>Angiopoietin-like 4 (ANGPTL4) is a hepatokine involved in metabolism and inflammation and has been implicated in oncogenesis, yet its relationship with cancer risk in humans remains unclear.</div></div><div><h3>Methods</h3><div>We analyzed 35,716 cancer-free UK Biobank participants with baseline plasma ANGPTL4. Multivariable Cox models and restricted cubic splines assessed associations with 24 site-specific incident cancers; bidirectional two-sample Mendelian randomization (MR) evaluated causality.</div></div><div><h3>Results</h3><div>During a median follow-up of 12.5 years, 9304 incident cancer cases occurred. Compared with the lowest quartile (Q1), the higher quartiles (Q2, Q3, and Q4) of ANGPTL4 levels were significantly associated with the risks of ten cancers, including cancers of the bladder, breast, cervix uteri, colorectum/anus, esophagus, kidney, liver, mesothelial/soft tissues, multiple myeloma, and ovary (hazard ratios ranging from 1.02 to 3.98). Risks generally increased across ANGPTL4 quartiles, and spline analyses supported approximately linear dose–response patterns. Adding ANGPTL4 to an age–sex model improved discrimination across several sites (ΔC-index 0–0.071), with statistical significance observed only for breast cancer. Associations were directionally consistent but heterogeneous by age, sex, and BMI. Forward MR provided no evidence that genetically proxied ANGPTL4 causally increases cancer risk. In reverse MR, genetic liability to liver cancer showed a nominal positive association with circulating ANGPTL4, suggesting ANGPTL4 may be elevated as part of tumor-related biology.</div></div><div><h3>Conclusions</h3><div>Higher circulating ANGPTL4 is associated with increased risk of multiple cancers, with sex-and tissue-specific heterogeneity. Although MR does not support a universal causal role, ANGPTL4 remains a promising pan-cancer biomarker for risk stratification and early prevention.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157089"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of the immune cell signature associated with the development of immune-related adverse event: Results from longitudinal immune profiling","authors":"Jiana Chen ,&nbsp;Xiaoyan Si ,&nbsp;Jiaqi Xu ,&nbsp;Ziyue Zhou ,&nbsp;Dan Yang ,&nbsp;Mengyuan Wang ,&nbsp;Li Zhang ,&nbsp;Naixin Liang ,&nbsp;Yunyun Fei ,&nbsp;Xu Jiang ,&nbsp;Huaxia Yang","doi":"10.1016/j.cyto.2025.157103","DOIUrl":"10.1016/j.cyto.2025.157103","url":null,"abstract":"<div><h3>Background</h3><div>The dynamics of peripheral immune cells during the development of immune-related adverse events (irAEs) remain incompletely characterized, underscoring the need to elucidate their temporal patterns to uncover immune disturbances and identify biomarkers.</div></div><div><h3>Methods</h3><div>In this prospective study, patients with lung cancer receiving immune checkpoint inhibitors (ICIs) were enrolled at Peking Union Medical College Hospital and were consecutively followed up for the development of irAEs. Comprehensive immune profiling by multicolor flow cytometry of peripheral blood samples collected at baseline (T0), early (T1, 1-3 weeks) and late (T2, 3-6 months) treatment, and at the onset of irAE (Tae) was performed. We utilized Mfuzz clustering analysis to characterize immune cell trajectories and calculated the change in cell frequencies (ΔT) from T0 to subsequent time points (ΔTae, ΔT1, and ΔT2) to identify time-dependent immune signatures predictive of irAE occurrence, severity, and specific organ involvement.</div></div><div><h3>Results</h3><div>Among the 60 lung cancer patients who received ICIs, 26 (43.3 %) developed irAEs. Mfuzz clustering highlighted the distinct dynamics of CD8^mid T cells and CD14⁺CD16⁻HLA-DR^hi monocytes during ICIs therapy. During early treatment, the irAE group showed a greater increase in CD8⁺CTLA-4⁺ T cells and greater reductions in both total CD8⁺ T cells and double-negative B (DNB) cells. At ΔT2, the irAE group exhibited significantly greater alterations in CD4⁺CD25⁺ T cells, CD4⁺HLA-DR⁺ T cells, CD14⁺CD16⁻HLA-DR^hi monocytes, and CD8^mid T cells. At ΔTae, patients with irAEs exhibited a significant expansion of non-switched memory (NSM) B cells and a reduction in CD3⁺ T cells, whereas non-irAE patients showed opposite trends. Stratified analysis confirmed that the ΔT of NSM B cells, CD8⁺CTLA-4⁺ T cells, DNB cells, CD4⁺CD25⁺ T cells, and CD14⁺CD16⁻HLA-DR^hi monocytes aligned with both clinical severity and specific organ involvement of irAEs.</div></div><div><h3>Conclusion</h3><div>The distinct dynamics of cellular signatures during irAEs development provide potential biomarkers associated with the development of irAEs and shed novel insights into immune disturbance.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157103"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic immune inflammation index, systemic inflammatory response index and pan-immune inflammation value in the prediction of idiopathic late-onset fetal growth restriction","authors":"Murat Levent Dereli ,&nbsp;Sadun Sucu ,&nbsp;Dilara Sarıkaya Kurt ,&nbsp;Ahmet Kurt ,&nbsp;Fahri Burçin Fıratlıgil ,&nbsp;Tuğba Ağbal ,&nbsp;Ali Turhan Çağlar","doi":"10.1016/j.cyto.2025.157081","DOIUrl":"10.1016/j.cyto.2025.157081","url":null,"abstract":"<div><h3>Background</h3><div>Fetal growth restriction (FGR) is a major pregnancy complication associated with stillbirth, perinatal morbidity, mortality and long-term consequences for the offspring. Therefore, its prediction, early detection and appropriate follow-up are essential components of prenatal care. In most cases, also referred to as late-onset idiopathic FGR (IL-FGR), symptoms appear after 34 weeks and the underlying pathology is unclear. Our aim was to investigate the relationship between altered inflammation and pathogenesis using inflammatory indices calculated from the complete blood count.</div></div><div><h3>Methods</h3><div>We conducted a retrospective case-control study in a large tertiary hospital between 2022 and 2023. Data from all participants at the time of screening for fetal aneuploidy and structural anomalies at 11–14 weeks were retrospectively reviewed and compared.</div></div><div><h3>Results</h3><div>A total of 106 eligible participants with IL-FGR and 106 women who experienced a healthy prenatal and perinatal period were included. Neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), pan-immune inflammation value (PIV) and SIRI/body-mass index (BMI) were significantly higher in the IL-FGR group (<em>p</em> &lt; 0.001 for all). SIRI/BMI with a cut-off value of &gt;76.3 × 10³ × kg/μL × m² (64 % sensitivity, 80 % specificity) showed the best discriminatory performance for IL-FGR prediction. Correlation analysis of gestational age-adjusted parameters with these indices showed a negative correlation with birthweight, suggesting that higher values of the inflammatory indices at the 11–14-week aneuploidy screening are associated with a greater likelihood of severe IL-FGR.</div></div><div><h3>Conclusions</h3><div>Our results suggest an association between high SII, SIRI, PIV and SIRI/BMI and an increased risk of future IL-FGR. SIRI/BMI may be an important component of regression models that could be used in the future as a screening tool for predicting FGR. However, our results require further validation by future studies to confirm the specific clinical implications of these indices.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157081"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between pan-immune inflammatory values and chronic kidney disease: An insight originating from the NHANES database","authors":"Zihan Liu ,&nbsp;Haiyang Wang ,&nbsp;Zihao Zhang ,&nbsp;Wenyan Wang ,&nbsp;Chen Wang ,&nbsp;Xingfu Lu ,&nbsp;Zhepeng Liu ,&nbsp;Tao Shen","doi":"10.1016/j.cyto.2025.157095","DOIUrl":"10.1016/j.cyto.2025.157095","url":null,"abstract":"<div><h3>Background</h3><div>Pan-immune-inflammatory value (PIV) is a novel inflammatory biomarker that integrates four immune cell types to generate a holistic inflammatory profile. Its comprehensive nature has positioned PIV as a clinically relevant predictor. Chronic kidney disease (CKD), characterized by irreversible kidney damage, is increasingly recognized as an inflammatory disorder, yet the clinical utility of PIV in CKD remains underexplored.</div></div><div><h3>Methods</h3><div>This cross-sectional study analyzed data from 39,156 participants in the 2011–2018 National Health and Nutrition Examination Survey (NHANES) cycles. Weighted multivariate logistic regression models were employed to evaluate the association between PIV levels and CKD prevalence. Non-linear relationships were assessed using restricted cubic spline (RCS) analyzes with smoothed curve fitting. Subgroup analyses and interaction tests were conducted to examine potential effect modification by demographic and clinical confounders.</div></div><div><h3>Results</h3><div>Multivariate logistic regression revealed a significant positive association between elevated PIV and CKD prevalence. RCS analyzes demonstrated a J-shaped relationship, suggesting that the risk of developing chronic kidney disease increases when PIV is elevated. Subgroup interactions were non-significant, suggesting consistent associations across strata of gender, educational attainment, comorbidity status, or lifestyle factors.</div></div><div><h3>Conclusion</h3><div>This study identifies a non-linear positive association between PIV and incident CKD that is independent of traditional confounders. RCS analyzes demonstrated a J-shaped relationship, suggesting that when PIV is elevated, there is also an increased risk of developing chronic kidney disease. These findings support PIV as a complementary biomarker for CKD risk stratification and warrant mechanistic studies investigating its role in renal inflammation pathways, alongside prospective validation in cross-sectional study.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157095"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-7 promotes naïve T cell motility to enable T cell scanning of dendritic cells in the LN","authors":"Janie R. Byrum ,&nbsp;Kimberly A. Morrissey ,&nbsp;David J. Torres ,&nbsp;Sreenivasa Rao Oruganti ,&nbsp;Judy L. Cannon","doi":"10.1016/j.cyto.2025.157105","DOIUrl":"10.1016/j.cyto.2025.157105","url":null,"abstract":"<div><div>IL-7 is a key regulator of naïve T cell homeostasis including T cell development, survival, and proliferation. IL-7 is highly expressed in lymph nodes (LNs), and we investigated the potential for IL-7 to drive naïve T cell movement in LNs. We show that IL-7 can mediate high speed T cell movement in vitro and in LNs. Downstream of IL-7R, T cell motility requires JAK1/3 and STAT5 activation, but mTOR signaling is not required. Using computational modeling and imaging of T cell motion in lymph nodes through two photon microscopy, we find that IL-7R-mediated motility accounts for T cell localization near DCs in the LN, suggesting that IL-7 can regulate naive T cell contacts with DCs. These data demonstrate a novel role for the IL-7/IL-7R pathway in controlling rapid T cell motility, showing that IL-7/IL-7R mediated T cell motion can facilitate efficient T cell-DC interactions in the LN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157105"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared inflammation in takotsubo syndrome and sepsis: Lipocalin-2 mediates neutrophil infiltration and cardiac damage","authors":"Yuxi Huang ,&nbsp;Piaorong Zeng ,&nbsp;Tianmin Liu ,&nbsp;Mei Xu ,&nbsp;Wenyi Tang ,&nbsp;Fangyuan Cheng ,&nbsp;Zhijuan Zhou ,&nbsp;Bairong Chen ,&nbsp;Kan Liu ,&nbsp;TouKun Chong ,&nbsp;Jian Chen","doi":"10.1016/j.cyto.2025.157102","DOIUrl":"10.1016/j.cyto.2025.157102","url":null,"abstract":"<div><h3>Background</h3><div>Takotsubo syndrome (TTS) and sepsis often co-occur with poor outcomes, yet their underlying molecular mechanisms remain to be elucidated. Transcriptomic analysis is employed to detect diagnostic biomarkers and reveal shared pathophysiological mechanisms in sepsis-associated TTS.</div></div><div><h3>Methods</h3><div>Myocardial gene expression data (TTS, sepsis, and controls) from GEO were analyzed to identify shared differentially expressed genes. WGCNA and PPI networks were used for candidate gene selection. Key genes were further refined using random forest and LASSO algorithms. Immune cell infiltration was assessed using CIBERSORT. Myocardial injury and gene expression in rat models were evaluated using HE staining, TUNEL assay, immunohistochemistry, qPCR, and Western blotting. Clinical validation was conducted using plasma samples from the China TTS Registry. <em>t</em>-tests and ANOVA were conducted via GraphPad Prism 8 software. A <em>P</em>-value &lt; 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Lipocalin-2 (LCN2) was recognized as an important biomarker through WGCNA, PPI network analysis, and machine learning algorithms, showing strong predictive performance. Its expression was significantly associated with neutrophil infiltration and myocardial injury in TTS. Consistent with the bioinformatics findings, the TTS-sepsis comorbidity model showed elevated mRNA and protein levels of LCN2 in myocardial tissue, accompanied by increased neutrophil infiltration and severe cardiac injury. Clinical validation confirmed elevated plasma LCN2 levels in patients with sepsis-associated TTS, correlating with neutrophil counts, NT-proBNP, and cTnI levels.</div></div><div><h3>Conclusion</h3><div>LCN2 is identified as a key inflammatory mediator linking neutrophil-driven inflammation to myocardial injury in sepsis-associated TTS, with dual potential as a diagnostic biomarker and therapeutic target.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157102"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated experimental and computational approaches to analyze TNF superfamily ligand–receptor interactions","authors":"Anne-Laure Favier ,&nbsp;Cyril Salama ,&nbsp;Chloé Cervera ,&nbsp;Diane Riccobono ,&nbsp;Krisztina Nikovics","doi":"10.1016/j.cyto.2025.157100","DOIUrl":"10.1016/j.cyto.2025.157100","url":null,"abstract":"<div><div>The TNF superfamily, composed of cytokines and their receptors, plays a central role in regulating immune responses, apoptosis, inflammation, and tissue regeneration. TNF itself is a key orchestrator of the cytokine cascade in many diseases and is often described as a “master regulator.” It engages in complex ligand-receptor interactions, making the study of these dynamics essential for the development of new therapeutic strategies.</div><div>This review summarizes the current experimental and computational tools used to study ligand–receptor interactions within the TNF superfamily, highlighting both their strengths and limitations. Particular attention is given to methods for analyzing protein–protein interactions, which are fundamental to deciphering the regulatory functions of this family. While traditional <em>in vitro</em>, <em>in vivo</em>, and <em>in situ</em> approaches have confirmed numerous authentic ligand–receptor pairs, <em>in silico</em> analyses reveal a much broader landscape of predicted interactions. These computational predictions do not represent experimentally validated binding events; rather, they indicate possible ligand–receptor compatibilities based on structural homology, interface similarity, and docking-derived binding energies. Such predictions suggest that the TNF interaction network may be more extensive than previously recognized, underscoring the need for systematic experimental validation to uncover additional biologically relevant interactions.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157100"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMAD signaling in cancer: integrative roles in tumor progression, immune evasion, and therapeutic resistance","authors":"Hai Zhao ,&nbsp;Fan Yang ,&nbsp;Jiaxin Yang ,&nbsp;Sheng Yang","doi":"10.1016/j.cyto.2025.157090","DOIUrl":"10.1016/j.cyto.2025.157090","url":null,"abstract":"<div><div>Transforming growth factor-beta (TGF-β)/SMAD signaling exerts pleiotropic effects in cancer, orchestrating epithelial–mesenchymal transition (EMT), immune evasion, stemness, and therapeutic resistance. While canonically regarded as tumor-suppressive, emerging data reposition SMAD proteins, particularly SMAD2, SMAD3, and SMAD4, as central effectors of pro-tumorigenic reprogramming in advanced malignancies. Here, we delineate the multifaceted contributions of SMAD signaling across tumor-intrinsic and microenvironmental contexts, highlighting post-translational regulation, immune remodeling, and crosstalk with non-coding RNAs. We show how SMADs mediate dynamic EMT programs, modulate innate and adaptive immune landscapes, and drive chemoresistance through transcriptional and metabolic rewiring. In the tumor microenvironment (TME), SMAD-driven axes involving macrophages, neutrophils, and CAFs reinforce immune suppression and metastasis. Moreover, engineering SMAD pathways in CAR-T and NK cells enhances immunotherapeutic efficacy. We also identify SMAD-based transcriptional and epigenetic signatures with prognostic and predictive utility across multiple tumor types. This integrative review provides a unified framework for understanding the SMAD signaling network as both a mechanistic driver and therapeutic vulnerability in cancer.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157090"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}