{"title":"GPNMB Suppresses Inflammation and Extracellular Matrix Degradation in Nucleus Pulposus Cells by Inhibiting Pro-Inflammatory Cytokine Production and Activation of the NF-κB Signaling Pathway.","authors":"Jun Zheng, Yaodong Song, Bing Yu","doi":"10.1089/jir.2025.0022","DOIUrl":"10.1089/jir.2025.0022","url":null,"abstract":"<p><p>Lumbar disc herniation is primarily caused by intervertebral disc degeneration (IVDD). Nucleus pulposus (NP) cell dysfunction leads to pro-inflammatory cytokines secretion increase, causing extracellular matrix (ECM) degradation. ECM is essential for maintaining normal disc function. Glycoprotein (Transmembrane) Nmb (GPNMB) is strongly associated with inflammation, and its expression and effects in IVDD are unclear. We categorized 40 clinically collected IVDD samples using the magnetic resonance imaging (MRI)-based Pfirrmann grading system. GPNMB mRNA expression was notably suppressed in patients with severe IVDD compared with patients with mild IVDD. Increased GPNMB mRNA expression correlated with decreased Interleukin-6 (IL-6) expression and increased collagen type II (COL2A1) expression levels. We utilized lentivirus to overexpress GPNMB in IL-1β-induced NP cells to explore its function in IVDD. GPNMB overexpression inhibited pro-inflammatory cytokines Tumor necrosis factor-alpha and IL-6 secretion in IL-1β-induced NP cells, while anti-inflammatory cytokine IL-10 content was increased. In addition, GPNMB overexpression inhibited NP ECM degradation by decreasing ECM-degrading enzymes matrix metalloproteinases-3/13 and a disintegrin and metalloproteinase with thrombospondin motifs-4/5 <i>in vitro</i>. Mechanism studies revealed that GPNMB was bound to CD44, a receptor expressed on the NP cell surface. GPNMB overexpression inhibited nuclear factor-κB (NF-κB) p65 phosphorylation and nuclear translocation <i>in vitro</i>, possibly through CD44. In conclusion, GPNMB suppressed the expression of pro-inflammatory cytokines and ECM degradation in NP cells by inhibiting activation of NF-κB.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"238-246"},"PeriodicalIF":1.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015098","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}
Zhaorong Yue, Fei Xie, Ruyue Wang, Xin Wang, Hongyu Li
{"title":"Lienal Polypeptide Decreases Immune Thrombocytopenia in a Mouse Model by Upregulating Cytokine Production and Increasing the Levels of CD4<sup>+</sup>, CD8<sup>+</sup>, and T Regulatory Cells.","authors":"Zhaorong Yue, Fei Xie, Ruyue Wang, Xin Wang, Hongyu Li","doi":"10.1089/jir.2024.0256","DOIUrl":"10.1089/jir.2024.0256","url":null,"abstract":"<p><p>Primary immune thrombocytopenia (ITP) is a condition marked by immune-mediated inadequate platelet production or excessive destruction. This study investigates the effects of Lienal polypeptide injection (LP) on T lymphocyte subgroups in the spleen and thymus, megakaryocyte counts in the bone marrow, and cytokine levels related to megakaryocyte development in mice with antibody-induced ITP, aiming to elucidate potential therapeutic mechanisms. We first assessed the effects of LP on Meg-01 megakaryocytic cells regarding proliferation, apoptosis, and differentiation using Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays, Western blot analysis, and flow cytometry for apoptosis and CD41 expression as a differentiation marker. Following this, LP was administered intraperitoneally at 60 mg/(kg·d) for 11 days to ITP mice. We quantified peripheral blood platelets and bone marrow megakaryocytes, measured spleen and thymus indices, and assessed serum levels of stem cell factor (SCF), interleukin-3 (IL-3), interleukin-6 (IL-6), and platelet factor-4 (PF-4) via enzyme-linked immunosorbent assay (ELISA). Flow cytometry quantified T-helper cells (CD4<sup>+</sup>), cytotoxic T cells (CD8<sup>+</sup>), and regulatory T cells (Tregs). LP significantly induced apoptosis in Meg-01 cells while not markedly affecting differentiation. In ITP mice, LP effectively prevented platelet decline without affecting megakaryocyte counts or maturity. Increased SCF, IL-3, and IL-6 levels, alongside decreased PF-4 levels, correlated with enhanced platelet production. Moreover, CD4<sup>+</sup>/CD8<sup>+</sup> ratios and Treg populations increased, contributing to reduced platelet destruction. In conclusion, LP exerts a protective effect in ITP by modulating SCF, IL-3, IL-6, and PF-4 levels and restoring the balance of T cell subtypes, elucidating its therapeutic potential.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"214-226"},"PeriodicalIF":1.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670119","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":"KLF13 Attenuates Lipopolysaccharide-Induced Alveolar Epithelial Cell Damage by Regulating Mitochondrial Quality Control via Binding PGC-1α.","authors":"Qiong Xi, Lin Liu, Qin Zhao, Shan Zhu","doi":"10.1089/jir.2023.0234","DOIUrl":"10.1089/jir.2023.0234","url":null,"abstract":"<p><p>Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"227-237"},"PeriodicalIF":1.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476790","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}
Farhad Seif, Karrar Hadi Kadhim, Milad Ahmadaghdami, Paria Bayati, Somayeh Sadani, Homa Davoodi, Ali Memarian, Somayeh Ghorbani, Yasser Bagheri
{"title":"Differential Expression of Th17-Related Cytokines in Patients of Chronic Kidney Disease with and Without Systemic Lupus Erythematosus.","authors":"Farhad Seif, Karrar Hadi Kadhim, Milad Ahmadaghdami, Paria Bayati, Somayeh Sadani, Homa Davoodi, Ali Memarian, Somayeh Ghorbani, Yasser Bagheri","doi":"10.1089/jir.2024.0265","DOIUrl":"10.1089/jir.2024.0265","url":null,"abstract":"<p><p>Dysregulation of immune cells and cytokines, particularly T helper 17 (Th17) cells and their associated cytokines, is implicated in the pathogenesis of both systemic lupus erythematosus (SLE) and chronic kidney disease (CKD). This study aimed to investigate the serum levels of Th17-related cytokines (interleukin [IL]-17A, IL-21, IL-22, and IL-23) in CKD patients with and without SLE and explore their potential role in disease progression. A total of 118 participants were included, comprising 78 patients with CKD (stages 3-5) and 40 healthy controls. Cytokine levels were measured using enzyme-linked immunosorbent assay kits. Patients with CKD exhibited significantly lower IL-21 levels and higher IL-22 and IL-17A levels compared with controls, while patients with end-stage renal disease showed elevated IL-21 and IL-23 levels. Among SLE-negative nephrotic patients, IL-23 and IL-17A were significantly upregulated, whereas SLE-positive nephrotic patients had increased IL-22 and IL-17A levels. In addition, IL-21 and IL-17A were significantly correlated in patients with CKD, suggesting a potential immunoregulatory interplay. These findings indicate that Th17-related cytokines are differentially expressed depending on CKD stage and SLE status, potentially influencing immune responses, inflammation, and kidney fibrosis. Understanding alterations of these cytokines may aid in identifying targeted therapeutic, particularly for patients with CKD at risk of SLE-related complications.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"205-213"},"PeriodicalIF":1.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127873","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}
Analía Toledano, Ana Caratozzolo, Romina Lanfranchi, Mayra Martinez, Marian Chacoff, Carolina Carballo, Laura B Talarico, María M Contrini, Eduardo Luis López
{"title":"Role of Interleukin-8 in Hemolytic Uremic Syndrome Severity in Children with Shiga Toxin-Producing <i>Escherichia Coli</i> Infection.","authors":"Analía Toledano, Ana Caratozzolo, Romina Lanfranchi, Mayra Martinez, Marian Chacoff, Carolina Carballo, Laura B Talarico, María M Contrini, Eduardo Luis López","doi":"10.1089/jir.2025.0031","DOIUrl":"https://doi.org/10.1089/jir.2025.0031","url":null,"abstract":"<p><p>We aimed to measure serum concentrations of interleukin (IL) 8, tumor necrosis factor-α (TNF-α), IL-6, IL-1β, and human neutrophil gelatinase-associated lipocalin (N-gal) in children with Shiga toxin-producing <i>Escherichia coli</i> (STEC) infection to determine the inflammatory cytokine profile and the role of these molecules in hemolytic uremic syndrome (HUS) development and severity. Three groups of patients with evidence of STEC infection were incorporated: bloody diarrhea (BD), patients with HUS requiring dialysis (HUSD), and patients with HUS and no dialysis requirement (HUSND). Serum samples were assayed for cytokines and N-gal using immunoassays. Thirty-six children were enrolled: 13 with BD, 10 with HUSND, and 13 with HUSD. We found significantly higher levels of IL-8, TNF-α, IL-6, and N-gal in patients with HUSD compared to patients with BD. Only TNF-α levels were significantly higher in patients with HUSND than in patients with BD. Higher IL-8 and N-gal levels were evidenced in HUSD than in patients with HUSND at the initial stages of disease. Principal component analysis revealed that children with HUSD exhibited an immune profile different from the other study groups. These results suggest a possible involvement of IL-8 in disease severity in patients with STEC-HUS. Furthermore, our results indicate a potential role of N-gal in HUS development.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180316","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}
Lars B Eriksson, Mats Eriksson, Torsten Gordh, Anders Larsson
{"title":"Significant Associations Between Blood Cell Counts and a Large Number of Salivary Cytokines, Chemokines, and Growth Factors.","authors":"Lars B Eriksson, Mats Eriksson, Torsten Gordh, Anders Larsson","doi":"10.1089/jir.2025.0048","DOIUrl":"https://doi.org/10.1089/jir.2025.0048","url":null,"abstract":"<p><p>The association between local oral inflammation and cardiovascular risk has been extensively studied, with results indicating a bidirectional relationship. The aim of the present study was to investigate the associations between blood cells and a large number of salivary cytokines, chemokines, and growth factors. The study consisted of 165 individuals who were referred to the Oral and Maxillofacial Surgery clinic at Falun County hospital, Sweden, for surgical removal of impacted lower third molar. The study subjects did not have any known inflammatory disorders. Complete blood cell counts were analyzed using the routine laboratory at Falun Hospital, Falun, Sweden. Proteomic analysis of 92 inflammation-related protein biomarkers in saliva was performed using a multiplex proximity extension assay. After adjustment for multiplicity testing using the false discovery rate approach, there remained significant association between several saliva cytokines, chemokines, and growth factors and white blood cell counts (<i>n</i> = 19), neutrophil counts (<i>n</i> = 18), erythrocyte counts (<i>n</i> = 13), hemoglobin concentrations (<i>n</i> = 20), erythrocyte volume fractions (<i>n</i> = 22), and platelet counts (<i>n</i> = 12). There are several significant associations between local inflammatory cytokines in the oral cavity and blood cell parameters indicating a relationship between local and systemic inflammatory activity.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110917","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":"Epigenome-Wide DNA Methylation Profiling of Peripheral Blood Shows Lymphocyte Dysfunction in Children with Kawasaki Disease.","authors":"Jayakanthan Kabeerdoss, Rakesh Kumar Pilania, Taru Goyal, Abarna Thangaraj, Manpreet Dhaliwal, Surjit Singh","doi":"10.1089/jir.2025.0029","DOIUrl":"https://doi.org/10.1089/jir.2025.0029","url":null,"abstract":"<p><p>Kawasaki disease (KD) is an acute childhood vasculitis, commonly seen in children under the age of five. Despite extensive research over the past five decades, the pathogenesis of KD remains elusive. The objective of this epigenetic reanalysis study is to delineate common pathways involved in KD using a bioinformatics approach. Array datasets from the Gene Expression Omnibus repository were extracted and subjected to analysis using the Chip Analysis Methylation Pipeline in the R statistical tool for the identification of differential methylation probes and differential methylation regions. Adaptive immune genes <i>CD8B, RAG1, IL-7R, STAT1</i>, and <i>CCR7</i> were significantly hypermethylated in acute KD as compared to healthy controls. Gene enrichment analysis showed that genes involved in T-cell receptor activation and differentiation, antigen processing and presentation of MHC class I were hypermethylated, whereas neutrophil degranulation was hypomethylated in the acute phase of KD as compared to healthy controls. The proportion of neutrophils significantly increased, while the proportions of CD4 T-cells and CD8 T-cells decreased in the peripheral blood of children with acute KD as compared to healthy controls. Reduced proportions of CD4 T cells and CD8 T cells, as well as hypermethylation of their genes, have been observed in the peripheral blood of patients with acute KD. [Figure: see text].</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015430","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":"Beyond Traditional Publishing: Social Media as a Catalyst for Biomedical Research Dissemination and Collaboration.","authors":"Jaleel Shujath","doi":"10.1089/jir.2025.0074","DOIUrl":"https://doi.org/10.1089/jir.2025.0074","url":null,"abstract":"<p><p>The expansion of social media has fundamentally transformed biomedical research dissemination and collaboration, particularly within the interferon and cytokine research community. This paper explores recent trends (2024-2025) that have amplified the role of platforms such as Twitter (now \"X\"), LinkedIn, Mastodon, Threads, and Bluesky. These tools have facilitated rapid knowledge exchange, democratized access to scientific discourse, enabled diverse voices to participate meaningfully, and fostered cross-disciplinary and global collaborations. Additionally, the integration of preprint repositories like bioRxiv and medRxiv, along with the evolution of open access publishing, further accelerates the accessibility and immediacy of scientific communication. Despite evident benefits, the rapid dissemination facilitated by social media also poses ethical challenges, including concerns about misinformation, premature dissemination of preliminary data, and privacy considerations. Practical strategies for researchers and institutions to effectively navigate these platforms responsibly are presented, aiming to optimize the impact of social media on scientific discovery and public engagement.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028148","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}
Komal Saleem, Hira Raheem Akbar, Zuzana Macek Jilkova, Ahmad Ali Shahid, Muhammad Idrees, Samia Afzal
{"title":"Polymorphisms in IL-10- and IL-22-Binding Protein Genes as Genetic Predictors of the Direct-Acting Antivirals Treatment Response in Patients with Chronic Hepatitis C Virus.","authors":"Komal Saleem, Hira Raheem Akbar, Zuzana Macek Jilkova, Ahmad Ali Shahid, Muhammad Idrees, Samia Afzal","doi":"10.1089/jir.2025.0005","DOIUrl":"10.1089/jir.2025.0005","url":null,"abstract":"<p><p>Cytokines are crucial in controlling inflammation during viral infection, particularly infection with the hepatitis C virus (HCV). Cytokine genetic polymorphisms can change how the immune system responds to this infection. We investigated how the HCV infection treatment was affected by single nucleotide polymorphisms in these genes. The goal of this study was to examine any connections between the cytokine gene polymorphisms for interleukins (IL)-22-binding protein rs6570136, as well as IL-10 rs1800872 and rs1878672 in the Pakistani population and responsiveness to direct-acting antivirals (DAAs) treatment. This study evaluated 155 participants, which included 55 patients who achieved sustained virologic response (SVR), 40 relapse patients, and 60 healthy controls, to assess and compare the clinical parameters. The SVR and relapse groups were compared for their allelic and genotypic frequencies. We discovered that the SVR and the relapse groups had significantly different genotype frequencies for IL-10 rs1800872 and IL-22BP rs6570136 in the Pakistani population. The G/G genotype in rs6570136 and A/A genotype in rs1800872 were significantly associated with relapse following DAA therapy, with <i>P</i> values 0.002 and 0.0004, respectively. In contrast, rs1878672 showed no significant correlation with HCV relapse, <i>P</i> = 0.63.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"196-204"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663655","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}
Mohammad Reza Ataherian, Nasim Hafezi, Elaheh Ferdosi-Shahandashti, Fatemeh Sarina Abdinia
{"title":"IFN-γ Approaches in Tumor Suppression, Its Challenges, and Future Directions: A Review of Recent Advances.","authors":"Mohammad Reza Ataherian, Nasim Hafezi, Elaheh Ferdosi-Shahandashti, Fatemeh Sarina Abdinia","doi":"10.1089/jir.2024.0259","DOIUrl":"10.1089/jir.2024.0259","url":null,"abstract":"<p><p>IFN-γ is recognized as an immunoregulatory cytokine due to its dual role in both accelerating and dampening immunological responses. Accordingly, in the context of tumor immunotherapy, the therapeutic outcome of IFN-γ is contingent upon factors such as dosage and the expression status of downstream signaling molecules. Furthermore, the coadministration of IFN-γ with various immunestimulatory agents, including anticheckpoint inhibitors, chemotherapeutic agents, and herbal-based medicines, may potentially overcome the IFN-γ-related challenges and enhance the response rate. We decipher the mechanisms of tumor cell eradication facilitated by IFN-γ, the last achievements in IFN-γ-mediated tumor immunotherapy across various cancers, and the strategies to address the failure of IFN-γ-based tumor immunotherapy. Unraveling the molecular mechanisms that lead to failure in IFN-γ-based antitumor actions could assist in pinpointing therapeutic agents that target the immune-modulatory features of IFN-γ, thereby increasing the antitumor response rate.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"164-173"},"PeriodicalIF":1.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364819","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}