Frontiers in Immunology最新文献

{"title":"Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin.","authors":"Ziwei Yang, Tixin Han, Ruibin Yang, Yinuo Zhang, Yifei Qin, Jialu Hou, Fei Huo, Zhuan Feng, Yaxin Ding, Jiali Yang, Gang Zhou, Shijie Wang, Xiaohang Xie, Peng Lin, Zhi-Nan Chen, Jiao Wu","doi":"10.3389/fimmu.2025.1531874","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1531874","url":null,"abstract":"<p><strong>Introduction: </strong>Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc-, induces ferroptosis. Imidazole ketone erastin (IKE), an inhibitor of the system Xc- functional subunit solute carrier family 7 member 11 (SLC7A11), is an effective and metabolically stable inducer of ferroptosis with potential in vivo applications. However, tumor cells exhibited differential sensitivity to IKE-induced ferroptosis. The intrinsic factors determining sensitivity to IKE-induced ferroptosis remain to be explored to improve its efficacy.</p><p><strong>Methods: </strong>Bulk RNA-sequencing data from hepatocellular carcinoma (HCC) and normal liver tissues were collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Differentially expressed genes were identified and intersected with the ferroptosis-related genes (FRGs) listed in the FerrDb database, yielding the identification of 13 distinct FRGs.</p><p><strong>Results: </strong>A ferroptosis signature index model (Risk Score) was developed to predict HCC prognosis. And SLC7A11 and NAD(P)H quinone dehydrogenase 1 (NQO1) were identified as candidate FRGs indicating poor prognosis of HCC. Dicoumarol (DIC), an inhibitor of NQO1, was subsequently employed to assess its sensitizing effects on IKE in HCC treatment. In HCC cell lines and the subcutaneous xenograft model, the combined suppression of SLC7A11 and NQO1 significantly enhanced the inhibitory effect on tumor growth by inducing ferroptosis.</p><p><strong>Discussion: </strong>In conclusion, our findings demonstrate that DIC sensitized HCC cells to IKE-induced ferroptosis in HCC. Moreover, the identification of potential drugs that enhance the susceptibility of HCC cells to ferroptosis could provide novel therapeutic strategies for the treatment of HCC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1531874"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Unraveling the molecular mechanisms of cytokine signaling in regulating inflammatory diseases.","authors":"Jian Zheng, Huawei Mao, Wai Po Chong","doi":"10.3389/fimmu.2025.1563469","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1563469","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563469"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIPK1 in necroptosis and recent progress in related pharmaceutics.","authors":"Kunhou Yao, Zhihao Shi, Fengya Zhao, Cong Tan, Yixin Zhang, Hao Fan, Yingzhe Wang, Xingwang Li, Jun Kong, Qun Wang, Dingxi Li","doi":"10.3389/fimmu.2025.1480027","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1480027","url":null,"abstract":"<p><p>Necroptosis is a programmed form of cell death. Receptor-interacting serine/threonine protein kinase l (RIPK1) is a crucial protein kinase that regulates the necroptosis pathway. Increased expression of death receptor family ligands such as tumor necrosis factor (TNF) increases the susceptibility of cells to apoptosis and necroptosis. RIPK1, RIPK3, and mixed-lineage kinase-like domain (MLKL) proteins mediate necrosis. RIPK1-mediated necroptosis further promotes cell death and inflammation in the pathogenesis of liver injury, skin diseases, and neurodegenerative diseases. The N-terminal kinase domain of RIPK1 is significant in the induction of cell death and can be used as a vital drug target for inhibitors. In this paper, we outline the pathways of necroptosis and the role RIPK1 plays in them and suggest that targeting RIPK1 in therapy may help to inhibit multiple cell death pathways.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1480027"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing risk stratification in kidney transplantation: integrating HLA-derived T-cell epitope and B-cell epitope matching algorithms for enhanced predictive accuracy of HLA compatibility.","authors":"Matthias Niemann, Benedict M Matern, Gaurav Gupta, Bekir Tanriover, Fabian Halleck, Klemens Budde, Eric Spierings","doi":"10.3389/fimmu.2025.1548934","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1548934","url":null,"abstract":"<p><strong>Introduction: </strong>The immune-mediated rejection of transplanted organs is a complex interplay between T cells and B cells, where the recognition of HLA-derived epitopes plays a crucial role. Several algorithms of molecular compatibility have been suggested, each focusing on a specific aspect of epitope immunogenicity.</p><p><strong>Methods: </strong>Considering reported death-censored graft survival in the SRTR dataset, we evaluated four models of molecular compatibility: antibody-verified Eplets, Snow, PIRCHE-II and amino acid matching. We have statistically evaluated their co-dependency and synergistic effects between models systematically on 400,935 kidney transplantations using Cox proportional hazards and XGBoost models.</p><p><strong>Results: </strong>Multivariable models of histocompatibility generally outperformed univariable predictors, with a combined model of HLA-A, -B, -DR matching, Snow and PIRCHE-II yielding highest AUC in XGBoost and lowest BIC in Cox models. Augmentation of a clinical prediction model of pre-transplant parameters by molecular compatibility metrics improved model performance particularly considering long-term outcomes.</p><p><strong>Discussion: </strong>Our study demonstrates that the use of multiple specialized molecular HLA matching predictors improves prediction performance, thereby improving risk classification and supporting informed decision-making in kidney transplantation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1548934"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune monitoring of trabectedin therapy in refractory soft tissue sarcoma patients - the IMMUNYON study.","authors":"Paulo Rodrigues-Santos, Jani Sofia Almeida, Luana Madalena Sousa, Patrícia Couceiro, António Martinho, Joana Rodrigues, Ruben Fonseca, Manuel Santos-Rosa, Paulo Freitas-Tavares, José Manuel Casanova","doi":"10.3389/fimmu.2025.1516793","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1516793","url":null,"abstract":"<p><p>Soft tissue sarcomas (STS) encompass over 50 histologic subtypes, representing more than 1% of solid tumors. Standard treatments include surgical resection and therapies such as anthracyclines or trabectedin for advanced cases, though challenges persist due to the tumor microenvironment's complexity and limited immune profiling data. This study evaluates Trabectedin therapy in 22 refractory STS patients, analyzing progression-free survival (PFS) and immune responses. Immune monitoring included deep immunophenotyping (200+ parameters), gene expression profiling (103 genes), and soluble proteome analysis (99 analytes). Using RECIST1.1 criteria, 68.2% of patients achieved stable disease (SD), while 31.8% exhibited progression disease (PD). Therapy duration revealed 59.1% treated for less than 12 months (<12M) and 40.9% for 12 or more months (≥12M). A significant PFS improvement was observed in SD versus PD patients (p=0.0154), while therapy duration showed no effect (p=0.5433). PD patients showed reduced eosinophils (p<0.05) and Th2 cells (p<0.05). Gene expression analysis identified changes in BTRC (decreased), IFNA1 (increased), and IL9 (increased) in PD versus SD patients (p<0.05). Patients treated ≥12M exhibited increased activated HLA-DR Th2 cells (p<0.05) and decreased exhausted B cells and NK cell subsets (p<0.05). Principal component and hierarchical clustering analyses identified distinct immune profiles associated with RECIST1.1 and therapy duration, underscoring immune profiling's role in understanding treatment responses. These findings support further research into immune monitoring for future clinical trials.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1516793"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Beyond PD-1: novel checkpoint receptors and ligands as targets for immunotherapy.","authors":"Jesse Haramati, Fabiola Solorzano-Ibarra, Dallas B Flies","doi":"10.3389/fimmu.2025.1563383","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1563383","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563383"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hyper-acute immune hemolytic anemia induced by contrast medium was successfully treated with eculizumab: a case report.","authors":"Sabine Hermann, Karina Althaus, Migdat Mustafi, Beate Mayer, Peter Rosenberger, Helene Anna Haeberle, Alice Bernard","doi":"10.3389/fimmu.2025.1464014","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1464014","url":null,"abstract":"<p><p>Contrast medium is frequently associated with allergic reactions and kidney dysfunction. However, contrast media can induce hemolytic anemia with a broad spectrum of hemolytic manifestations. We report a 38-year-old patient with very severe immune hemolytic anemia after the application of iomeprol due to a CT of the thorax/abdomen. In this case report, we illustrate the diagnostics and treatment of life-threatening hemolytic anemia induced by a contrast medium that was successfully treated with eculizumab.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1464014"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemotherapy with bleomycin, oxaliplatin, or cisplatin in mouse tumor models, from tumor ablation to <i>in situ</i> vaccination.","authors":"Katja Uršič Valentinuzzi, Urška Kamenšek, Simona Kranjc Brezar, Chloe Heranney, Tilen Komel, Simon Buček, Maja Čemažar, Gregor Serša","doi":"10.3389/fimmu.2025.1470432","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1470432","url":null,"abstract":"<p><strong>Introduction: </strong>In addition to its direct cytotoxic effects, ablative therapies as electrochemotherapy (ECT) can elicit indirect antitumor effects by triggering immune system responses. Here, we comprehensively analyzed this dual effectiveness of intratumoral ECT with chemotherapeutic drugs bleomycin (BLM), oxaliplatin (OXA), and cisplatin (CDDP). Our aim was to determine if ECT can act as <i>in situ</i> vaccination and thereby induce an abscopal effect. By evaluating ECT's potential for <i>in situ</i> vaccination, our goal was to pave the way for future advancements for its combination with emerging (immuno)therapies, leading to enhanced responses and outcomes.</p><p><strong>Methods: </strong>We employed two mouse tumor models, the immunologically cold B16F10 melanoma and 4T1 mammary carcinoma, to explore both local and systemic (i.e., abscopal) antitumor effects following equieffective intratumoral ECT with BLM, OXA, and CDDP. Through histological analyses and the use of immunodeficient and metastatic (for abscopal effect) mouse models, we identified and compared both the cytotoxic and immunological components of ECT's antitumor efficiency, such as immunologically recognizable cell deaths (immunogenic cell death and necrosis) and immune infiltrate (CD11⁺, CD4⁺, CD8⁺, GrB⁺).</p><p><strong>Results: </strong>Differences in immunological involvement after equieffective intratumoral ECT were highlighted by variable kinetics of immunologically recognizable cell deaths and immune infiltrate across the studied tumor models. Particularly, the 4T1 tumor model exhibited a more pronounced involvement of the immune component compared to the B16F10 tumor model. Variances in the antitumor (immune) response were also detected based on the chemotherapeutic drug used in ECT. Collectively, ECT demonstrated effectiveness in inducing <i>in situ</i> vaccination in both tumor models; however, an abscopal effect was observed in the 4T1 tumor model only.</p><p><strong>Conclusions: </strong>This is the first preclinical study systematically comparing the immune involvement in intratumoral ECT's efficiency using three distinct chemotherapeutic drugs in mouse tumor models. The demonstrated variability in immune response to ECT across different tumor models and chemotherapeutic drugs provides a basis for future investigations aimed at enhancing the effectiveness of combined treatments.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1470432"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Recognition of <i>Staphylococcus aureus</i> by the pattern recognition molecules langerin, mannan-binding lectin, and surfactant protein D: the influence of capsular polysaccharides and wall teichoic acid.","authors":"Kirstine Mejlstrup Hymøller, Stig Hill Christiansen, Anders Grønnegaard Schlosser, Uffe B Skov Sørensen, Jean C Lee, Steffen Thiel","doi":"10.3389/fimmu.2025.1568032","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1568032","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1504886.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1568032"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Hiding features in myeloid cells: metabolism preference in different disease models.","authors":"Jie Shen, DuoYao Cao","doi":"10.3389/fimmu.2025.1565258","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1565258","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1565258"},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}