Frontiers in Immunology最新文献

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Local and systemic immunological response in feline chronic gingivostomatitis: a critical review. 猫慢性龈口炎的局部和全身免疫反应:一个重要的回顾。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1572631
Rafael S Lopes, Pedro P Carvalho, Maria A Pires, Paulo Rodrigues-Santos, Eduardo Costa, João F Requicha
{"title":"Local and systemic immunological response in feline chronic gingivostomatitis: a critical review.","authors":"Rafael S Lopes, Pedro P Carvalho, Maria A Pires, Paulo Rodrigues-Santos, Eduardo Costa, João F Requicha","doi":"10.3389/fimmu.2025.1572631","DOIUrl":"10.3389/fimmu.2025.1572631","url":null,"abstract":"<p><strong>Introduction: </strong>A comprehensive understanding of the oral immune response in feline chronic gingivostomatitis (FCGS) is crucial for veterinarians to improve clinical and therapeutic decisions. This critical review addresses the local and systemic immune responses associated with FCGS.</p><p><strong>Methods: </strong>A comprehensive database search was conducted using the PubMed/MEDLINE database, resulting in 3,358 studies. Following a rigorous screening process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 17 publications were included in this review.</p><p><strong>Results: </strong>The local immune response in FCGS is primarily evaluated through histopathological and immunohistochemical analyses of oral biopsy samples, and by analysis of saliva. Histopathological analysis reveals a dense lymphoplasmacytic infiltration within the mucosa, indicating chronic inflammation. Immunohistochemical staining identifies increased numbers of mast cells, altered expression of immunoglobulins (IgG, IgM, and IgA) and presence of immunomarkers (CD3+, CD4+, CD8+ T cells and Mott cells), indicating immune dysregulation. Systemic immune features of FCGS are investigated in blood samples through flow cytometry, polymerase chain reaction, and enzyme-linked immunosorbent assay. A consistent finding is an increased level of pro-inflammatory cytokines (IL-6, TNF-α, and IFN-γ), indicating intense systemic immune activation. Neutrophilia, disrupted CD4/CD8 T-cell ratio, a reduction in CD21+ B cells and alterations in regulatory T cells expressing FOXP3, suggests chronic immune regulation dysfunction.</p><p><strong>Discussion: </strong>The findings highlight a complex relationship between local and systemic immune responses, by significant alterations in T cell subsets, pro-inflammatory cytokines, and immunoglobulin expression. The frequent presence of CD3+, CD4+, and CD8+ T cells, along with impaired regulatory T cell (FOXP3+) function, suggests that dysregulated cell-mediated immunity is a key factor in the pathogenesis of FCGS. Elevated systemic immunomarkers (IL-6, TNF-α, and IFN-γ), provide further evidence of a chronic immune activation state. The immunopathological similarities observed between FCGS and human oral lichen planus reinforce the potential of FCGS individuals as a spontaneous model for comparative research. This review found that there is a lack of comprehensive information on the oral immune response of FCGS. Further observational and experimental studies focusing on the link between local and systemic immune responses are essential to fully understand the complexity and guide the development of novel, evidence-based therapeutic strategies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1572631"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185486","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}
引用次数: 0
Tumor-derived SEMA7A regulates fatty acid oxidation in the tumor-associated macrophages to promote the progression of non-small cell lung cancer. 肿瘤来源的SEMA7A调节肿瘤相关巨噬细胞中的脂肪酸氧化,促进非小细胞肺癌的进展。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1625208
Jia Wang, Yang Shao, Jiameng Zhang, Fangfang Han, Si Wang, Beixing Liu
{"title":"Tumor-derived SEMA7A regulates fatty acid oxidation in the tumor-associated macrophages to promote the progression of non-small cell lung cancer.","authors":"Jia Wang, Yang Shao, Jiameng Zhang, Fangfang Han, Si Wang, Beixing Liu","doi":"10.3389/fimmu.2025.1625208","DOIUrl":"10.3389/fimmu.2025.1625208","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is an aggressive cancer with a poor prognosis. Despite the success of therapies for NSCLC, more investigations of new biomarkers for patient selection are urgently needed. Semaphorin 7A (SEMA7A), a soluble tumor-derived molecule, can modulate the proliferation, invasion and angiogenesis of multiple types of cancers. However, whether SEMA7A contributes to the progression of NSCLC is still unknown. In this study, by using bioinformatics analysis and an experimental murine tumor model, we found that the expression levels of SEMA7A were elevated in the human NSCLC and positively correlated with the poor prognosis. Knockdown of SEMA7A in cancer cells may suppress NSCLC progression, in parallel with a diminished M2 polarization in the tumor microenvironment (TME). In fact, SEMA7A may increase the polarization of tumor-associated macrophages (TAMs) toward the M2 phenotype in an ITGB1-dependent manner. Fatty acid oxidation in macrophages seems to be essential for the ability of SEMA7A to promote M2 polarization. Blockade of fatty acid oxidation may reverse the immunosuppressive phenotype of TAMs and the outcomes of NSCLC. Our findings provide experimental evidence that SEMA7A may act as a regulatory factor for macrophage lipid metabolism, which influences the polarization status of TAMs.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1625208"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185705","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}
引用次数: 0
SIFD-associated TRNT1 deficiency unveils importance of TSPO during macrophage antibacterial and antiviral responses. sifd相关的TRNT1缺失揭示了TSPO在巨噬细胞抗菌和抗病毒反应中的重要性。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1497766
Duale Ahmed, Angelo Slade, Thet Fatica, Stephen Baird, Krishna Bhattarai, Thérèse Atallah, Edana Cassol, Martin Holcik
{"title":"SIFD-associated TRNT1 deficiency unveils importance of TSPO during macrophage antibacterial and antiviral responses.","authors":"Duale Ahmed, Angelo Slade, Thet Fatica, Stephen Baird, Krishna Bhattarai, Thérèse Atallah, Edana Cassol, Martin Holcik","doi":"10.3389/fimmu.2025.1497766","DOIUrl":"10.3389/fimmu.2025.1497766","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondria support cellular biosynthetic and bioenergetic demands and mediate cell signaling. Their dysfunction is implicated in a wide range of diseases, including congenital disorders. One such disorder, sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD), is caused by mutations in the tRNA-nucleotidyltransferase enzyme TRNT1. While SIFD is known to affect immune function, the role of macrophages-key mediators between innate and adaptive immunity-remains underexplored.</p><p><strong>Methods: </strong>To investigate the impact of TRNT1 deficiency on macrophage function, we employed siRNA-mediated knockdown of TRNT1 in murine RAW264.7 macrophages. Cells were stimulated with lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly (I:C)) to mimic bacterial and viral infections, respectively. Cytokine production was measured, and mitochondrial reprogramming was assessed. Bioinformatic analysis was conducted to identify TRNT1-dependent transcripts, focusing on mitochondrial-associated proteins. Functional rescue experiments were performed using TSPO ligands and TSPO overexpression.</p><p><strong>Results: </strong>TRNT1 knockdown impaired inflammatory cytokine production in response to both LPS and Poly (I:C). This correlated with diminished mitochondrial reprogramming, suggesting a mechanistic link between TRNT1 activity and macrophage effector function. Transcriptomic analysis identified the mitochondrial translocator protein (TSPO) as a TRNT1-dependent gene. TSPO expression was differentially regulated following stimulation in TRNT1-deficient cells. While TSPO ligand activation failed to restore cytokine production, TSPO overexpression prior to TRNT1 knockdown selectively rescued the inflammatory response to Poly (I:C), but not LPS. This rescue was associated with enhanced recruitment of VDAC to the mitochondrial permeability transition pore via TSPO.</p><p><strong>Discussion: </strong>Our findings reveal that TRNT1 is critical for pathogen-specific mitochondrial reprogramming in macrophages, influencing their inflammatory capacity. The differential restoration of cytokine responses via TSPO overexpression underscores the complexity of mitochondrial signaling in immune regulation. These insights suggest that targeting mitochondrial pathways may offer a novel therapeutic strategy for managing immunodeficiency in SIFD.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1497766"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185678","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}
引用次数: 0
Advance in therapies targeting tumor-associated macrophages in ovarian cancer. 靶向肿瘤相关巨噬细胞治疗卵巢癌的研究进展。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1677839
Man Li, Yue Ma, Tinggeng Dai, Yongxin Wang, Ying Yue
{"title":"Advance in therapies targeting tumor-associated macrophages in ovarian cancer.","authors":"Man Li, Yue Ma, Tinggeng Dai, Yongxin Wang, Ying Yue","doi":"10.3389/fimmu.2025.1677839","DOIUrl":"10.3389/fimmu.2025.1677839","url":null,"abstract":"<p><p>Ovarian cancer remains the deadliest gynecologic malignancy, with its aggressive progression and therapeutic resistance heavily influenced by the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), the predominant immune infiltrates in OC, play pivotal roles in metastasis, immunosuppression, and chemoresistance by adopting a pro-tumoral M2 phenotype. Despite promising preclinical results, clinical translation faces challenges, such as on-target toxicity and incomplete understanding of TAM ontogeny in humans. This review summarizes the origins, heterogeneity, and functional plasticity of TAMs, emphasizing their mechanistic contributions to OC progression through epithelial-mesenchymal transition (EMT), angiogenesis, and immune evasion. We outline the emerging evidence that TAMs drive platinum resistance via exosomal signaling and metabolic reprogramming, underscoring TAMs as central mediators of OC pathogenesis and treatment paradigms.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1677839"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080358","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}
引用次数: 0
A splicing-based multitissue association study of joint transcriptomes identified susceptibility genes for osteoarthritis. 基于剪接的关节转录组多组织关联研究确定了骨关节炎的易感基因。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1590008
Lantao Zhang, Fuxing Zhao, Hengheng Zhang, Xingbang Niu, Youliang Li, Chunxia Zhao, Jianhua Ding, Chaozheng Liu
{"title":"A splicing-based multitissue association study of joint transcriptomes identified susceptibility genes for osteoarthritis.","authors":"Lantao Zhang, Fuxing Zhao, Hengheng Zhang, Xingbang Niu, Youliang Li, Chunxia Zhao, Jianhua Ding, Chaozheng Liu","doi":"10.3389/fimmu.2025.1590008","DOIUrl":"10.3389/fimmu.2025.1590008","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a common chronic degenerative joint disease worldwide, which seriously affects the quality of life of patients and adds economic burden. Although genome-wide association studies (GWAS) have identified multiple genetic loci associated with OA, the functional mechanisms of these loci remain unclear. Transcriptome association studies (TWAS) combining gene expression and GWAS data have provided new perspectives to explore the genetic basis of OA.</p><p><strong>Methods: </strong>This study integrated cross-tissue and single-tissue TWAS analyses as well as single-cell sequencing data to identify and validate the key genes associated with OA. Cross- and single-tissue analyses were performed using the UTMOST, FUSION, and MAGMA methods, while single-cell sequencing was applied for the investigation of the expression characteristics, pseudotemporal trajectories, and cell-to-cell communication patterns of the latent transforming growth factor beta binding protein 1 (LTBP1) in different cell subtypes.</p><p><strong>Results: </strong>This study identified multiple candidate genes associated with OA, among which LTBP1 displayed a significant association in both cross-tissue and single-tissue analyses (FDR < 0.05) and was validated as a key regulator of the transforming growth factor-beta (TGF-β) signaling pathway. Single-cell sequencing revealed that LTBP1 was differentially expressed in different chondrocyte subtypes and was associated with high enrichment of the Notch signaling pathway. Pseudotemporal analysis revealed the dynamic regulatory role of LTBP1 in chondrocyte differentiation.</p><p><strong>Conclusion: </strong>Intercellular communication analysis revealed that cells with high LTBP1 expression activated diverse signaling pathways such as TGF-β and vascular endothelial growth factor (VEGF), suggesting that it may be involved in the pathogenesis of OA by regulating the formation of the extracellular matrix and the immune response.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1590008"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185508","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}
引用次数: 0
Arsenic sulfide enhances the therapeutic effect of hepatocellular carcinoma immunotherapy through STAT3-THBS1/CD47 pathway. 硫化砷通过STAT3-THBS1/CD47途径增强肝癌免疫治疗的疗效。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1612318
Ting Kang, Zhuowei Feng, Yu Cai, Ruizhe Huang, Ruiheng Wang, Zhiyi Liu, Shumin Lu, Shufeng Xie, Han Liu, Siyu Chen
{"title":"Arsenic sulfide enhances the therapeutic effect of hepatocellular carcinoma immunotherapy through STAT3-THBS1/CD47 pathway.","authors":"Ting Kang, Zhuowei Feng, Yu Cai, Ruizhe Huang, Ruiheng Wang, Zhiyi Liu, Shumin Lu, Shufeng Xie, Han Liu, Siyu Chen","doi":"10.3389/fimmu.2025.1612318","DOIUrl":"10.3389/fimmu.2025.1612318","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) represents a formidable challenge in oncology, with high mortality rates and limited therapeutic options, particularly for advanced-stage patients. While immunotherapy has shown promise, its efficacy in advanced HCC remains suboptimal, necessitating the exploration of more potent therapeutic strategies.</p><p><strong>Methods: </strong>The HCC cell lines underwent treatment with arsenic sulfide and/or anti-PD1, while HepG2/Hepa1-6 cells were transduced with lentiviruses for THBS1 overexpression or knockdown. The MTT assay, FACS, Western blotting, qRT-PCR, and ChIP were employed to assess proliferation, modulation of proteins and genes. Additionally, C57BL/6J mice were utilized <i>in vivo</i> to investigate the ability of arsenic sulfide to enhance the efficacy of anti-PD-1 therapy.</p><p><strong>Results: </strong>Here, we investigated the role of arsenic sulfide in HCC treatment and explored its potential synergistic effects and underlying mechanisms when combined with immunotherapy. First of all, using bioinformatics analysis and validation <i>in vitro</i>, we identified thrombospondin-1 (THBS1) as a key prognostic factor for HCC in Asian populations. Then, we demonstrated that arsenic sulfide inhibits HCC cell viability, induces apoptosis, and downregulates THBS1 expression. Furthermore, we observed that arsenic sulfide significantly enhances the anti-HCC effects of anti-PD-1 therapy. Mechanistic insights indicate that arsenic sulfide inhibits STAT3 phosphorylation, reduces THBS1 transcription, thereby disrupting the binding between tumor cell THBS1 and T cell CD47, consequently enhancing anti-PD-1 efficacy. Therefore, arsenic sulfide augments anti-PD-1 efficacy against HCC by inhibiting the STAT3-THBS1/CD47 pathway.</p><p><strong>Conclusions: </strong>Collectively, our findings elucidate the role of arsenic sulfide in conjunction with PD - 1 in HCC eradication and its underlying molecular mechanism, providing a precise scientific rationale and a robust theoretical basis for arsenic sulfide's application in HCC treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1612318"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185612","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}
引用次数: 0
Tumor-infiltrating lymphocytes and tumor-associated macrophages in cancer immunoediting: a targetable therapeutic axis. 肿瘤浸润淋巴细胞和肿瘤相关巨噬细胞在癌症免疫编辑中的作用:一个可靶向的治疗轴。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1655176
Sumon Mukherjee, Ahana Ghosh, Sourio Chakraborty, Udit Basak, Sumoyee Mukherjee, Tanya Das, Gaurisankar Sa
{"title":"Tumor-infiltrating lymphocytes and tumor-associated macrophages in cancer immunoediting: a targetable therapeutic axis.","authors":"Sumon Mukherjee, Ahana Ghosh, Sourio Chakraborty, Udit Basak, Sumoyee Mukherjee, Tanya Das, Gaurisankar Sa","doi":"10.3389/fimmu.2025.1655176","DOIUrl":"10.3389/fimmu.2025.1655176","url":null,"abstract":"<p><p>Immunotherapy has transformed the landscape of cancer treatment, offering hope to patients who were once considered beyond the reach of effective care. However, its success is restricted to a limited fraction of patients. This discrepancy in response is largely due to the complex and dynamic nature of the tumor immune-microenvironment. At the heart of this complexity is the concept of cancer immunoediting-a dynamic process through which the immune system both sculpts and is shaped by the tumor. This process unfolds in three key stages: Elimination, Equilibrium, and Escape, each representing a shifting balance between immune defenses and tumor adaptation. Central to this interaction are tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). TILs are frontline defenders in targeting tumor cells, while TAMs can either hinder or facilitate tumor growth based on their polarization. As cancer progresses, immune selection pressure induces phenotypic alterations that promote immune evasion, fostering an environment detrimental to effective immune response. This review explores the role of these immunological components in each phase of immunoediting and their impact on the efficacy or failure of immunotherapy. Gaining deeper insight into these interactions is crucial for developing advanced immunotherapies that reshape tumor microenvironment and expand the reach of immunotherapy to more patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1655176"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185697","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}
引用次数: 0
Impact of Fusobacterium nucleatum on immune cell interactions and gene expression in colorectal cancer: a retrospective cohort study. 结直肠癌中核梭杆菌对免疫细胞相互作用和基因表达的影响:一项回顾性队列研究。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1629014
Ronald Heregger, Florian Huemer, Richard Greil, Marina Canadas-Ortega, Gernot Posselt, Marieke E Ijsselsteijn, Christina Plattner, Dietmar Rieder, Zlatko Trajanoski, Anne Krogsdam, Eckhard Klieser, Daniel Neureiter, Silja Wessler, Lukas Weiss
{"title":"Impact of <i>Fusobacterium nucleatum</i> on immune cell interactions and gene expression in colorectal cancer: a retrospective cohort study.","authors":"Ronald Heregger, Florian Huemer, Richard Greil, Marina Canadas-Ortega, Gernot Posselt, Marieke E Ijsselsteijn, Christina Plattner, Dietmar Rieder, Zlatko Trajanoski, Anne Krogsdam, Eckhard Klieser, Daniel Neureiter, Silja Wessler, Lukas Weiss","doi":"10.3389/fimmu.2025.1629014","DOIUrl":"10.3389/fimmu.2025.1629014","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a major global health concern. The presence of <i>Fusobacterium nucleatum</i> (Fn) in CRC can promote cancer progression by modulating the immune response and creating an immunosuppressive environment.</p><p><strong>Methods: </strong>A cohort of 107 patients with localized CRC treated between 2005 and 2017 was analyzed, categorizing tumors as Fn-positive (Fn<sup>+</sup>) or Fn-negative (Fn<sup>-</sup>) using quantitative PCR. Patient characteristics, tumor characteristics and survival data were compared between groups. We further performed bulk RNA sequencing and gene set enrichment analysis to explore differential gene expression between Fn<sup>+</sup> and Fn<sup>-</sup> CRC. Spatial immune cell interactions within the tumor microenvironment were characterized using imaging mass cytometry (IMC) and quantified through Voronoi tessellation-derived mixing scores.</p><p><strong>Results: </strong>In 45 out of 107 patients (42%) tumors were classified as Fn<sup>+</sup>. Fn positivity was significantly associated with poor tumor differentiation (p=0.008) but did not significantly impact overall survival (OS; log-rank p = 0.099) or disease-free survival (DFS, log-rank p=0.595). Fn<sup>+</sup> tumors exhibited distinct immunological features: RNA sequencing identified significant downregulation of pathways involved in immune activation and antibacterial defenses. IMC demonstrated increased intratumoral interactions between immune cells, antigen-presenting cells, and tumor cells in Fn<sup>+</sup> tumors compared to Fn<sup>-</sup> tumors, though these differences were not observed at tumor margins. Furthermore, Fn persistence was confirmed in metastatic lesions, suggesting a potential role in tumor spread and disease progression.</p><p><strong>Discussion: </strong>Our findings suggest that Fn contributes to an immunosuppressive microenvironment in CRC, diminishing both antibacterial defense and anti-tumor immunity. Selective elimination of Fn may enhance treatment efficacy and warrants further investigation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1629014"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185102","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}
引用次数: 0
Elevating MHC I expression on tumor cells by nanovesicles loading tyrosine kinase inhibitors can improve the efficacy of cancer vaccines. 通过纳米囊泡装载酪氨酸激酶抑制剂提高肿瘤细胞MHC I的表达可以提高癌症疫苗的疗效。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1653533
Huimin Xie, Lin Ma, Xiaoli He, Songsong Zhao, Jin Wang, Ao Zhu, Changming Liu, Olga Piskareva, Chao Deng, Fenghua Meng, Mi Liu
{"title":"Elevating MHC I expression on tumor cells by nanovesicles loading tyrosine kinase inhibitors can improve the efficacy of cancer vaccines.","authors":"Huimin Xie, Lin Ma, Xiaoli He, Songsong Zhao, Jin Wang, Ao Zhu, Changming Liu, Olga Piskareva, Chao Deng, Fenghua Meng, Mi Liu","doi":"10.3389/fimmu.2025.1653533","DOIUrl":"10.3389/fimmu.2025.1653533","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer vaccines work through activating tumor-specific T cells, which can specifically attack cancer cells by recognizing antigens binding with Major-Histocompatibility-Complex I (MHC I) molecules. The downregulation or loss of MHC I expression on tumor cells can affect the efficacy of cancer vaccines.</p><p><strong>Methods: </strong>Herein, to increase the MHC I expression on tumor cells, a nanovesicle-based strategy was developed to improve the efficacy of  cancer vaccines. Several clinically applied medicines, such as tyrosine kinase inhibitors (TKIs), were screened for their capacity to upregulate MHC I.</p><p><strong>Results: </strong>Two TKIs, Sunitinib and Sorafenib, were found to be very effective in elevating MHC I expression, and they were encapsulated into redox-responsive nanovesicles respectively (SUN-KD10 or SOR-KD10), which demonstrated favourable tumor-targeting capabilities in the tumor microenvironment. Sunitinib or Sorafenib activates the IFNγ/STAT1 pathway, which improve the expression of MHC I. When combined with whole-tumor-antigen-loaded nanovaccines, these nanovesicle formulations elicited a synergistic antitumor effect in both breast cancer and melanoma mouse models. The tumors in the tumor-bearing mice treated with combined strategy grew more slowly and the survival times of such mice are significantly prolonged.</p><p><strong>Discussion: </strong>The studies demonstrated that more tumor-specific T cells were activated in the combined strategy treated mice, suggesting improved immune-mediated tumor clearance. This combinatorial approach provides a promising strategy to overcome immune evasion and to enhance the therapeutic outcomes of cancer vaccine-based immunotherapy by using clinical-applied medicines with cancer vaccines.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1653533"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185752","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}
引用次数: 0
Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment. 嵌合抗原受体t细胞装甲克服实体肿瘤微环境障碍的当前策略。
IF 5.9 2区 医学
Frontiers in Immunology Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI: 10.3389/fimmu.2025.1643941
Dorothy D Yang, William Macmorland, James N Arnold
{"title":"Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.","authors":"Dorothy D Yang, William Macmorland, James N Arnold","doi":"10.3389/fimmu.2025.1643941","DOIUrl":"10.3389/fimmu.2025.1643941","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy is a transformative immunotherapeutic approach, yet its application in solid tumors is hindered by the immunosuppressive tumor microenvironment (TME). The TME restricts T-cell trafficking, impairs effector functions, and promotes exhaustion through soluble factors, metabolic stress, and suppressive cell populations. Recent efforts to enhance CAR T-cell efficacy have focused on armoring strategies that 'reprogram' and 'boost' T-cell responses within the TME. These include engineered expression of dominant-negative receptors or cytokine-releasing constructs (such as IL-12 and IL-18) to reshape the local immune milieu and improve T-cell effector function, synthetic Notch receptors for inducible gene expression, and chemokine receptor knock-ins to improve tumor infiltration. Additional approaches aim to modulate intrinsic metabolic pathways to improve CAR T-cell persistence under hypoxic or nutrient-deprived conditions. Armoring strategies that recruit bystander or endogenous immune cells also activate broader anti-tumor immunity that prevents antigen escape and may induce more durable anti-tumor responses. This review highlights the molecular and cellular mechanisms by which current armoring strategies enhance CAR T-cell functions in solid tumors, offering a perspective on improving immune cell engineering for overcoming the hurdles encountered in deploying these therapies against solid cancers.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1643941"},"PeriodicalIF":5.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185793","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}
引用次数: 0
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