{"title":"Research Hotspots of Interferon Gamma in the Treatment of Lung Cancer: A Bibliometric Analysis Based on CiteSpace.","authors":"Zhen Lv, Jianjun Wu","doi":"10.1089/jir.2024.0242","DOIUrl":"10.1089/jir.2024.0242","url":null,"abstract":"<p><p>Interferon-gamma (IFN-γ) is an important cytokine associated with antitumor immunity and has been implicated in the pathogenesis and progression of lung cancer. Nevertheless, no bibliometric analyses have been published in this field to date, and thus we aim to address this gap in knowledge. A search of the Web of Science (WOS) for literature related to the treatment of lung cancer with IFN-γ was conducted from 2002 to 2024. The extracted information from the included articles was subjected to visual analysis, and network diagrams were generated using software such as CiteSpace and VOSviewer. In total, 589 articles related to the treatment of lung cancer with IFN-γ were included in WOS between 2002 and 2024. The number of articles and citation frequency generally showed an increasing trend year by year. The United States and the University of California are the countries and institutions with the largest number of articles. The researcher who made the largest contribution to this field was Xin Cai from China (6). The <i>Journal for ImmunoTherapy of Cancer</i> published the largest number of relevant papers in the field (16 papers, IF = 12.469). The research hotspots in the field of immune escape in recent years have been IFN-γ, mechanism, immune checkpoints, and microtumor inhibitors. The field of IFN-γ treatment of lung cancer is evolving at a rapid pace. The current research focus within this field is on elucidating the mechanism of IFN-γ treatment of lung cancer, investigating the role of immune checkpoint inhibitors, and examining the tumor microenvironment and other pertinent topics.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"109-118"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059375","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}
Sarah E Hickson, Eden Brekke, Johannes Schwerk, Indraneel Saluhke, Shivam Zaver, Joshua Woodward, Ram Savan, Jennifer L Hyde
{"title":"Sequence Diversity in the 3' Untranslated Region of Alphavirus Modulates IFIT2-Dependent Restriction in a Cell Type-Dependent Manner.","authors":"Sarah E Hickson, Eden Brekke, Johannes Schwerk, Indraneel Saluhke, Shivam Zaver, Joshua Woodward, Ram Savan, Jennifer L Hyde","doi":"10.1089/jir.2024.0229","DOIUrl":"10.1089/jir.2024.0229","url":null,"abstract":"<p><p>Alphaviruses (family Togaviridae) are a diverse group of positive-sense RNA (+ssRNA) viruses that are transmitted by arthropods and are the causative agent of several significant human and veterinary diseases. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs) are a family of RNA-binding IFN-stimulated genes (ISGs) that are highly upregulated following viral infection and have been identified as potential restrictors of alphaviruses. The mechanism by which IFIT1 restricts RNA viruses is dependent on self and non-self-discrimination of RNA, and alphaviruses evade this recognition via their 5' untranslated region (UTR). However, the role of IFIT2 during alphavirus replication and the mechanism of viral replication inhibition is unclear. In this study, we identify IFIT2 as a restriction factor for Venezuelan equine encephalitis virus (VEEV) and show that IFIT2 binds the 3' 3'UTR of the virus. We investigated the potential role of variability in the 3'UTR of the virus affecting IFIT2 antiviral activity by studying infection with VEEV. Comparison of recombinant VEEV clones containing 3'UTR sequences derived from epizootic and enzootic isolates exhibited differential sensitivity to IFIT2 restriction <i>in vitro</i> infection studies, suggesting that the alphavirus 3'UTR sequence may function in part to evade IFIT2 restriction. <i>In vitro</i> binding assays demonstrate that IFIT2 binds to the VEEV 3'UTR; however, in contrast to previous studies, VEEV restriction did not appear to be dependent on the ability of IFIT2 to inhibit translation of viral RNA, suggesting a novel mechanism of IFIT2 restriction. Our study demonstrates that IFIT2 is a restriction factor for alphaviruses and variability in the 3'UTR of VEEV can modulate viral restriction by IFIT2. Ongoing studies are exploring the biological consequences of IFIT2-VEEV RNA interaction in viral pathogenesis and defining sequence and structural features of RNAs that regulate IFIT2 recognition.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"133-149"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615687","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}
Brittany S Ulloa, Isaac Barber-Axthelm, Bryan Berube, Malcolm Duthie, Steve Reed, Ram Savan, Michael Gale
{"title":"Synthetic RIG-I-Agonist RNA Induces Death of Hepatocellular Carcinoma Cells.","authors":"Brittany S Ulloa, Isaac Barber-Axthelm, Bryan Berube, Malcolm Duthie, Steve Reed, Ram Savan, Michael Gale","doi":"10.1089/jir.2024.0195","DOIUrl":"10.1089/jir.2024.0195","url":null,"abstract":"<p><p>Retinoic acid-inducible gene I (RIG-I) is a critical sensor of viral RNA and is activated in response to binding to RNA containing exposed 5'-triphosphate (5'ppp) and poly-uridine to trigger innate immune activation and response including induction of type I and III interferons (IFNs). RIG-I signaling plays a key role in not only restricting RNA virus infection but also suppressing tumor progression via oncolytic signaling. We evaluated the actions of a specific RIG-I agonist RNA (RAR) as a potential therapeutic against model tumor cell lines representing hepatocellular carcinoma (HCC). RAR constitutes a synthetic-modified RNA motif derived from the hepatitis C virus genome that is specifically recognized by RIG-I and induces innate immune activation when delivered to cells. We found that RAR directs RIG-I-dependent signaling to drive HCC cell death. Analysis of knockout cell lines lacking RIG-I, mitochondrial activator of virus signaling, or IRF3 confirmed that RAR-induced cell death signaling propagates through the RIG-I-like receptor (RLR) pathway to mediate caspase activation and HCC cell death. RAR-induced cell death is potentiated by type I IFN. Thus, RAR actions trigger HCC cell death through RIG-I linkage of RLR, caspase, and IFN signaling programs. RAR offers a potent application in antitumor therapeutic strategies leveraging innate immunity against liver cancer.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"119-132"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408356","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}
Dharmendra Kumar Soni, Juan Cabrera-Luque, Swagata Kar, Anwar Ahmed, Chaitali Sen, Joseph Devaney, Roopa Biswas
{"title":"Suppression of miR-155 Attenuates Lung Cytokine Storm Induced by SARS-CoV-2 Infection.","authors":"Dharmendra Kumar Soni, Juan Cabrera-Luque, Swagata Kar, Anwar Ahmed, Chaitali Sen, Joseph Devaney, Roopa Biswas","doi":"10.1089/jir.2024.0253","DOIUrl":"10.1089/jir.2024.0253","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) is a deadly human viral disease with a high rate of infection, morbidity, and mortality. Although vaccines and antiviral treatments are available, hospitalizations remain steady, and concerns about long-term consequences persist. Therefore, there is a great urgency to develop novel therapies. Here, we analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Endogenous microRNAs (miRNAs, miRs) are key molecules in preventing viral entry and replication while building an antiviral cellular defense. Our study reveals that miR-155 expression is elevated in patients with COVID-19. Using a mouse model transgenic for human angiotensin-converting enzyme receptor 2, we evaluated the potential of anti-miR-155 therapy. Treating SARS-CoV-2-infected mice with anti-miR-155 significantly reduced miR-155 expression, improved survival, and slightly increased body weight. Notably, these mice showed altered expression of cytokines in the lungs. These findings suggest anti-miR-155 could be a promising therapy to mitigate the cytokine storm and long-lasting symptoms induced by SARS-CoV-2 infection, improving public health outcomes and enhancing global pandemic preparedness.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"150-161"},"PeriodicalIF":1.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414570","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":"https://doi.org/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":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-21","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}
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":"https://doi.org/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":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-19","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}
Brianda Amezcua-Guerra, Luis M Amezcua-Castillo, Jazmín A Guerra-López, Kietseé Díaz-Domínguez, Héctor González-Pacheco, Luis M Amezcua-Guerra
{"title":"Cytokine-Based Validation of the Inflammation-Based Risk Score in Patients with ST-Segment Elevation Myocardial Infarction.","authors":"Brianda Amezcua-Guerra, Luis M Amezcua-Castillo, Jazmín A Guerra-López, Kietseé Díaz-Domínguez, Héctor González-Pacheco, Luis M Amezcua-Guerra","doi":"10.1089/jir.2024.0163","DOIUrl":"10.1089/jir.2024.0163","url":null,"abstract":"<p><p>This study aimed to validate an inflammation-based risk score in patients with ST-segment elevation myocardial infarction (STEMI) by examining their cytokine profiles. Upon admission, patients were evaluated for systemic inflammation using a risk score that assigned points based on specific biomarkers: 1 point for leukocyte count ≥9.3 × 10³ cells/μL, 2 points for high-sensitivity C-reactive protein (hsCRP) ≥13.0 mg/L, and 3 points for serum albumin ≤3.6 g/dL. Patients were categorized into three groups: no inflammation (0 points, <i>n</i> = 13), mild inflammation (1-2 points, <i>n</i> = 35), and severe inflammation (3-6 points, <i>n</i> = 26). Serum levels of 16 key cytokines were measured. Patients with higher risk scores showed elevated interleukin (IL)-6 levels (19.6 vs. 8.5 vs. 6.8 pg/mL; <i>P</i> = 0.021) and decreased interferon-γ-induced protein-10 (IP-10) levels (73.4 vs. 68.8 vs. 112.2 pg/mL; <i>P</i> = 0.011). IL-6 was positively correlated with hsCRP (ρ 0.307) and negatively correlated with albumin (ρ -0.298), while IP-10 was negatively correlated with leukocyte count (ρ -0.301). No other cytokines showed significant association with the risk score. Higher inflammation scores were also associated with an increased incidence of major adverse cardiovascular events, particularly acute heart failure. This study underscores the association between the inflammation-based risk score and cytokine levels, specifically IL-6 and IP-10, in patients with STEMI.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"91-98"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361658","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":"Acknowledgment of Reviewers 2024.","authors":"","doi":"10.1089/jir.2024.19874.revack","DOIUrl":"https://doi.org/10.1089/jir.2024.19874.revack","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"45 3","pages":"107"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630368","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}
Gabriela Athziri Sánchez-Zuno, Richard Bucala, Jorge Hernández-Bello, Claudia Azucena Palafox-Sánchez, Alexis Missael Vizcaíno-Quirarte, José Francisco Muñoz-Valle
{"title":"Distinctive Macrophage Migration Inhibitory Factor Receptor Patterns and Soluble Biomarkers in Rheumatoid Arthritis: Unveiling Key Associations with Disease Activity.","authors":"Gabriela Athziri Sánchez-Zuno, Richard Bucala, Jorge Hernández-Bello, Claudia Azucena Palafox-Sánchez, Alexis Missael Vizcaíno-Quirarte, José Francisco Muñoz-Valle","doi":"10.1089/jir.2024.0184","DOIUrl":"10.1089/jir.2024.0184","url":null,"abstract":"<p><p>We previously reported the peripheral blood cell patterns of expression for the migration inhibitory factor (MIF) canonical (CD74/CD44) and noncanonical receptors (CXCR2, CXCR4, and CXCR7) in rheumatoid arthritis (RA) patients and correlated this with clinical biomarkers and disease activity. This study aimed to evaluate the expression of these receptors alongside the serum levels of CXCL12 and CXCL8 (ligands for CXCR2, CXCR4, and CXCR7), which potentially regulate the action of these receptors and the influence the downstream effects of MIF. Additionally, we evaluated soluble levels of MIF, as well as its soluble cognate receptor (sCD74), in the serum of RA patients and control subjects (CS). Our findings revealed distinctive membrane expression patterns of MIF receptors in active (moderate and high disease activity) and non-active (low activity and remission) RA patients. Furthermore, RA patients exhibited elevated serum sCD74 levels, which correlated with disease activity, and elevated CXCL12 levels, which correlated with rheumatoid factor titers. Regarding serum CXCL8 and MIF levels, we observed higher CXCL8 levels in RA patients compared to CS, while MIF levels did not significantly differ between groups or by disease activity. The circulating sCD74/MIF ratio was elevated in RA patients, particularly in cases of moderate disease activity. Our study also indicated that treatment protocols did not significantly impact circulating MIF levels or the expression of its receptors. This study extends previous findings by supporting a role for sCD74 in downregulating MIF action and in the potential value of the sCD74/MIF ratio as a disease biomarker in RA.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"99-106"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364818","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":"Immunology Research in Latin America.","authors":"David L Woodland","doi":"10.1089/jir.2025.0024","DOIUrl":"10.1089/jir.2025.0024","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"83-84"},"PeriodicalIF":1.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382691","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}