Frontiers in Immunology最新文献

{"title":"Antibody-drug conjugates as game changers in bladder cancer: current progress and future directions.","authors":"Fei Zhang, Sheng Li","doi":"10.3389/fimmu.2025.1591191","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1591191","url":null,"abstract":"<p><strong>Introduction: </strong>Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic modality in oncology, offering unprecedented precision in targeting tumor cells while sparing healthy tissues. In bladder cancer, a malignancy with high recurrence rates and limited treatment options, ADCs have demonstrated remarkable efficacy by targeting specific tumor-associated antigens such as NECTIN-4 and Human Epidermal Growth Factor Receptor 2 (HER2). This review provides a comprehensive evaluation of the current landscape of ADC-based therapies for bladder cancer, focusing on their mechanisms of action, clinical efficacy, and safety profiles.</p><p><strong>Methods: </strong>We systematically analyze 232 clinical trials from 2004 to 2025, revealing a significant upward trend in ADC research, particularly following the Food and Drug Administration's (FDA) accelerated approval of Enfortumab vedotin in 2019.</p><p><strong>Results: </strong>Our findings highlight the predominance of HER2, NECTIN4, and PD-1 as the most extensively studied molecular targets, with a growing interest in combining ADCs with immune checkpoint inhibitors. Geographically, the United States and China lead in ADC clinical trials, reflecting robust research investment and infrastructure.</p><p><strong>Discussion: </strong>espite the promising advancements, challenges such as toxicity management, patient stratification, and trial design remain critical. This review underscores the importance of continued innovation in ADC technology and personalized approaches to overcome these limitations, ultimately paving the way for more effective and safer treatment options for bladder cancer patients. The future of ADC therapy in bladder cancer is bright, with immense potential to revolutionize the standard of care and improve patient outcomes globally.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1591191"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157879","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":"Mesenchymal stromal cells for steroid-refractory biopsy-proven grade III-IV acute Graft-versus-Host Disease with predominant gastrointestinal involvement.","authors":"Adomas Bukauskas, Renata Jucaitienė, Mindaugas Stoškus, Vilma Valčeckienė, Greta Bušmaitė, Artūras Slobinas, Linas Davainis, Inga Šlepikienė, Igoris Trociukas, Valdas Pečeliūnas, Laimonas Griškevičius, Andrius Žučenka","doi":"10.3389/fimmu.2025.1600019","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1600019","url":null,"abstract":"<p><strong>Introduction: </strong>Steroid-refractory acute Graft-versus-Host Disease (SR-aGVHD) is a potentially fatal complication occurring in approximately 60-70% of severe grade III-IV GVHD cases, with a higher incidence in patients with gastrointestinal (GI) involvement. GI aGVHD is associated with poor prognosis, with a 2-year overall survival (OS) rate of only 25% in patients with stage 3-4 GI involvement. Mesenchymal stromal cells (MSC) have emerged as a promising therapeutic option due to their favorable efficacy and safety profile. However, data on bone marrow (BM)-derived MSC use in biopsy-proven grade III-IV SR-aGVHD with GI involvement, particularly in stage 3-4 cases, remain limited.</p><p><strong>Methods: </strong>This prospective, observational, single-arm, single-center study assessed the efficacy and safety of BM-derived MSC for treating adult patients with biopsy-proven grade III-IV SR-aGVHD with predominant GI involvement. Early (1^st-2^nd) passage BM-derived MSC were administered weekly at a target dose of 1x10⁶ MSC/kg in two regimens: up to three (MSC3) and six doses (MSC6).</p><p><strong>Results: </strong>Fifty-seven adult patients with biopsy-proven III-IV grade SR-aGVHD (93% with GI involvement) received MSC treatment. The overall response rate (ORR) was 39% and 42% on Days 14 and 28, respectively, with no significant differences between the two MSC groups (Day 28 ORR 38% for MSC3 and 44% for MSC6). In patients with stage 3-4 GI involvement, the ORR was 26% and 36% at the corresponding time points with comparable efficacy between the two MSC groups (Day 28 ORR 31% for MSC3 and 38% for MSC6). Day 14 and Day 28 responders had significantly higher OS compared to non-responders (52% vs. 7%, p=0.000; 54% vs. 5%, p=0.000), with a comparable OS benefit observed in patients with stage 3-4 GI involvement (45% vs. 8%, p=0.005; 42% vs. 6%, p=0.005), respectively. MSC treatment had a favorable safety profile. The one, 5 and 10-year OS rates were 27%, 24%, and 24%, respectively.</p><p><strong>Conclusions: </strong>The grade III-IV SR-aGVHD patients, including cases with biopsy-proven severe GI involvement, had significantly better clinical outcomes if responses to MSC treatment were observed on Days 14 and 28. Intensified MSC administration schedule has failed to improve the clinical outcomes. MSC studies focusing on aGVHD prevention and (or) first-line treatment in combination with other agents should be considered.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1600019"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157889","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":"The promise of PD1/PDL1 targeted immunotherapy in locally advanced cervical cancer: a game-changer for patients outcome?","authors":"Fadila Kouhen, Adil El Ghanmi, Hanane Inghaoun, Hayat Miftah, Bouchra Ghazi, Abdallah Badou","doi":"10.3389/fimmu.2025.1573576","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1573576","url":null,"abstract":"<p><p>Locally advanced cervical cancer remains a significant therapeutic challenge, with high rates of recurrence and metastasis despite advances in chemoradiation. Immunotherapy, particularly immune checkpoint inhibitors targeting the PD-1/PD-L1 axis, has emerged as a promising strategy to enhance treatment efficacy. This review explores the integration of immunotherapy with standard chemoradiation, highlighting the potential of PD-1 inhibitors, such as pembrolizumab, in improving progression-free survival (PFS) among high-risk patients. Furthermore, the role of predictive biomarkers, including microsatellite instability (MSI) and tumor mutational burden (TMB), is examined to refine patient selection and personalize therapeutic approaches. Emerging strategies, including the use of nivolumab, ipilimumab, and maintenance immunotherapy, are also discussed. While preliminary clinical data are encouraging, further research is required to optimize treatment combinations, establish robust patient selection criteria, and enhance long-term outcomes in cervical cancer management.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1573576"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157974","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":"Clinical and mechanistic relevance of high-dimensionality analysis of the paediatric sepsis immunome.","authors":"Dandan Pi, Judith Ju Ming Wong, Katherine Nay Yaung, Nicholas Kim Huat Khoo, Su Li Poh, Martin Wasser, Pavanish Kumar, Thaschawee Arkachaisri, Feng Xu, Herng Lee Tan, Yee Hui Mok, Joo Guan Yeo, Salvatore Albani","doi":"10.3389/fimmu.2025.1569096","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1569096","url":null,"abstract":"<p><strong>Background: </strong>By employing a high-dimensionality approach, this study aims to identify mechanistically relevant cellular immune signatures that predict poor outcomes.</p><p><strong>Methods: </strong>This prospective study recruited 39 children with sepsis admitted to the intensive care unit and 19 healthy age-matched children. Peripheral blood mononuclear cells were studied with mass cytometry. Unique cell subsets were identified in the paediatric sepsis immunome and depicted with t-distributed stochastic neighbour embedding (tSNE) plots. Network analysis was performed to quantify interactions between immune subsets. Enriched immune subsets were included in a model for distinguishing sepsis and validated by flow cytometry in an independent cohort.</p><p><strong>Results: </strong>The median (interquartile range) age and paediatric sequential organ failure assessment (pSOFA) score in this cohort was 5.6(2.0, 11.3) years and 6.6 (IQR: 2.5, 10.1), respectively. High-dimensionality analyses of the immunome in sepsis revealed a loss of coordinated communication between immune subsets, particularly a loss of regulatory/inhibitory interaction between cell types, fewer interactions between cell subsets, and fewer negatively correlated edges than controls. Four independent immune subsets (CD45RA^-CX3CR1⁺CTLA4⁺CD4⁺ T cells, CD45RA^-17A⁺CD4⁺ T cells CD15⁺CD14⁺ monocytes, and Ki67⁺ B cells) were increased in sepsis and provide a predictive model for diagnosis with area under the receiver operating characteristic curve, AUC 0.90 (95% confidence interval, CI 0.82-0.98) in the discovery cohort and AUC 0.94 (95% CI 0.83-1.00) in the validation cohort.</p><p><strong>Conclusion: </strong>The sepsis immunome is deranged with loss of regulatory/inhibitory interactions. Four immune subsets increased in sepsis could be used in a model for diagnosis and prediction of poor outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1569096"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157884","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":"Glypican-3 regulated epithelial mesenchymal transformation-related genes in osteosarcoma: based on comprehensive tumor microenvironment profiling.","authors":"Jiaming Zhang, Wei Wang","doi":"10.3389/fimmu.2025.1566061","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1566061","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma (OS) is the most common primary bone malignancy, predominantly affecting children and adolescents. Current treatment approaches have limited efficacy, with a 5-year survival rate of approximately 60%. Epithelial-mesenchymal transition (EMT) plays a key role in the onset, progression, and metastasis of OS, potentially influencing patient prognosis.</p><p><strong>Methods: </strong>We screened EMT-related genes from multiple transcriptomic datasets of OS and performed unsupervised consensus clustering of EMT-related gene sets. Key EMT-related genes were identified using weighted gene co-expression network analysis (WGCNA) and intersected with differentially expressed genes (DEGs) between OS and normal tissue samples. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to screen candidate genes for developing a prognostic model. Single-cell RNA-Seq (scRNA-Seq) analysis was conducted on OS samples to identify cell populations expressing model genes. Functional validation was performed using si-GPC3 in the MG-63 cell line.</p><p><strong>Results: </strong>The EMT-based prognostic model demonstrated strong predictive capacity across several validation cohorts. The model effectively predicted immune-related features and immunotherapy responses in high-risk and low-risk patient groups. Seven primary cell types were identified from scRNA-Seq data of OS samples, with the osteoblast population showing the highest proportion of cells positive for model genes. The OS_C3 subpopulation exhibited significantly higher scores and included nine gene modules associated with metabolism, structural integrity, proliferation, differentiation, adhesion, migration, immune responses, inflammatory reactions, and signal transduction. The model genes also demonstrated prognostic value across various cancer types. Knockdown of GPC3 in MG-63 cells resulted in decreased proliferation and migration ability.</p><p><strong>Conclusion: </strong>This study provides new insights into the potential mechanisms of EMT in OS and its impact on the tumor immune microenvironment and response to immunotherapy. These findings may pave the way for novel personalized treatment strategies for OS patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1566061"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157965","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":"Potentiating T cell tumor targeting using a combination of TCR with a Siglec-7 based CSR.","authors":"Shiran Didi-Zurinam, Erel Katzman, Cyrille J Cohen","doi":"10.3389/fimmu.2025.1536868","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1536868","url":null,"abstract":"<p><strong>Introduction: </strong>Tumors may utilize different strategies to escape T cell immunosurveillance. Besides the overexpression of checkpoint ligands (such as PDL1) or the secretion of immunosuppressive agents, several studies have shown that cancer aberrant sialylation can, through interaction with selected receptors such as those from the Siglec family, neutralize NK and T cell function.</p><p><strong>Methods: </strong>Herein, we wanted to take advantage of the presence of inhibitory sialic acid ligands on the tumor cell surface to enhance T cell anti-tumor activity. To this end, we devised a novel chimeric receptor consisting of the extracellular portion of Siglec-7 and the intracellular portion of 41BB, which can convert inhibitory signals into stimulatory ones when expressed in human T-cells.</p><p><strong>Results: </strong>This co-stimulatory chimeric switch receptor (CSR), when co-expressed with a tumor-specific TCR, facilitated higher cytokine secretion and activation profiles following co-culture with tumor cells. Additionally, T cells equipped with Siglec-7 CSR demonstrated improved anti-tumor function <i>in vivo</i>.</p><p><strong>Discussion: </strong>Given the broad expression pattern of Siglec-7 ligands on tumor cells, our data suggest this CSR may act as a general adjuvant to boost TCR T cell function. Overall, this work provides an approach to improve engineered T-cell-based cancer treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1536868"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157966","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":"The recent advances in vaccine adjuvants.","authors":"Jiayin Xing, Xiangxiang Zhao, Xiaotian Li, Ren Fang, Mingrui Sun, Yang Zhang, Ningning Song","doi":"10.3389/fimmu.2025.1557415","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1557415","url":null,"abstract":"<p><p>Vaccine adjuvants, as key components in enhancing vaccine immunogenicity, play a vital role in modern vaccinology. This review systematically examines the historical evolution and mechanisms of vaccine adjuvants, with particular emphasis on innovative advancements in aluminum-based adjuvants, emulsion-based adjuvants, and nucleic acid adjuvants (e.g., CpG oligonucleotides). Specifically, aluminum adjuvants enhance immune responses through particle formation/antigen adsorption, inflammatory cascade activation, and T-cell stimulation. Emulsion adjuvants amplify immunogenicity via antigen depot effects and localized inflammation, while nucleic acid adjuvants like CpG oligonucleotides directly activate B cells and dendritic cells to promote Th1-type immune responses and memory T-cell generation. The article further explores the prospective applications of these novel adjuvants in combating emerging pathogens (including influenza and SARS-CoV-2), particularly highlighting their significance in improving vaccine potency and durability. Moreover, this review underscores the critical importance of adjuvant development in next-generation vaccine design and provides theoretical foundations for creating safer, effective adjuvant.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1557415"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157977","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":"Elevated platelet-to-lymphocyte ratio predicts poor clinical outcomes in non-muscle invasive bladder cancer: a systematic review and meta-analysis.","authors":"Wenfeng Hu, Jinze Liang, Jin Luo, Jie Fan, Huaichun Hu, Xinwen Wang, Peng Zhou, Xiaoyi Zhang, Jie Zhou","doi":"10.3389/fimmu.2025.1578069","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1578069","url":null,"abstract":"<p><strong>Introduction: </strong>The prognostic significance of platelet-to-lymphocyte ratio (PLR) in non-muscle invasive bladder cancer (NMIBC) remains controversial despite numerous investigations. This study aimed to systematically evaluate the prognostic value of PLR in NMIBC.</p><p><strong>Materials and methods: </strong>An extensive systematic search was executed utilizing four major electronic databases: Embase, PubMed, Web of Science, and Cochrane Library. The prognostic significance of PLR was assessed using pooled hazard ratios (HRs) with 95% CIs. Forest plots were used to present data visualization and statistical summaries, illustrating the effects of individual studies and the reliability of the pooled results. Funnel plot analysis and Egger's test were employed to evaluate the potential presence of publication bias. Sensitivity analysis was performed to assess the robustness of the pooled findings. Subgroup analysis and meta-regression were used to identify sources of heterogeneity.</p><p><strong>Results: </strong>Eleven retrospective studies encomprising 3,566 patients met the inclusion criteria. Elevated PLR notably correlated with inferior progression-free survival (PFS) (HR=2.132, 95% CI: 1.146-3.967, p=0.017) and relapse-free survival (RFS) (HR=1.732, 95% CI: 1.174-2.554, p=0.006). No statistically meaningful correlation emerged in cancer-specific survival (CSS) (HR=1.218, 95% CI: 0.800-1.854, p=0.358) or overall survival (OS) (HR=1.350, 95% CI: 0.611-2.983, p=0.459). Publication bias was detected in RFS analyses (Egger's test, P=0.010). Sensitivity analysis demonstrated that the pooled results were robust. Subgroup analysis and meta-regression identified geographic differences and patient characteristics as key sources of heterogeneity in RFS outcomes. Subgroup analysis indicated that geographic differences and sample size were potential sources of heterogeneity in PFS results.</p><p><strong>Discussion: </strong>This study comprehensively analyzed 11 studies and 3,566 NMIBC cases and found that elevated PLR was significantly associated with poorer RFS and PFS, suggesting that PLR can be used as a prognostic biomarker for the management of NMIBC. The prognostic value of PLR may be related to immune regulation and inflammatory response in the tumor microenvironment; nevertheless, further studies are needed to elucidate its mechanism and establish its clinical application.</p><p><strong>Conclusions: </strong>This study demonstrates that elevated PLR serves as an independent predictor of poor PFS and RFS in NMIBC patients. As a cost-effective biomarker, PLR shows promise in risk stratification and treatment planning. However, large-scale prospective studies are warranted to validate these findings and establish standardized cut-off values.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024621307 <b>, identifier CRD42024621307.</b></p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1578069"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157951","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":"Reversing VTN deficiency inhibits the progression of pancreatic cancer and enhances sensitivity to anti-PD1 immunotherapy.","authors":"Siqi Zhao, Zhaofeng Gao, Lingyu Hu, Yihan Li, Xiaoguang Wang, Xiaoping Li, Minjie Chen, Fei Chen, Zhengwei Song","doi":"10.3389/fimmu.2025.1578870","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1578870","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer, a highly lethal malignancy with limited therapeutic options, necessitates the identification of novel prognostic biomarkers and therapeutic targets. The extracellular matrix protein vitronectin (VTN) has been implicated in tumor progression, but its specific role in pancreatic cancer progression and immunotherapy response remains unclear.</p><p><strong>Methods: </strong>This study employed an integrative approach combining single-cell RNA sequencing, analysis of public databases, and functional assays. <i>In vitro</i> experiments assessed the impact of VTN knockdown and overexpression on pancreatic cancer cell proliferation, invasion, and migration. Mechanistic investigations explored associations between VTN expression and immune regulatory factors. A syngeneic mouse subcutaneous tumor model evaluated the therapeutic efficacy of VTN overexpression combined with anti-PD1 immunotherapy.</p><p><strong>Results: </strong>VTN was significantly downregulated in pancreatic cancer tissues compared to normal tissues. Lower VTN levels correlated with poorer overall survival. VTN knockdown promoted pancreatic cancer cell proliferation, invasion, and migration <i>in vitro</i>, whereas VTN overexpression suppressed these phenotypes. VTN expression was linked to immune regulatory pathways. High VTN levels predicted improved survival in patients receiving anti-PD1/PD-L1 therapy. In a mouse model, VTN overexpression inhibited tumor growth and synergized with anti-PD1 therapy to enhance antitumor efficacy, suggesting combinatorial therapeutic potential.</p><p><strong>Conclusions: </strong>This study identifies VTN as a dual-functional regulator in pancreatic cancer, acting as both a suppressor of tumor progression and a modulator of immunotherapy response. These findings position VTN as a prognostic biomarker and a therapeutic target to sensitize pancreatic tumors to anti-PD1-based immunotherapy, providing a potential strategy for overcoming treatment resistance in this aggressive malignancy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1578870"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157970","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":"IL-10 and IL-6/IL-10 as predictive biomarkers for treatment response in non-infectious uveitis.","authors":"Rodrigo A Valenzuela, Fabian Vega-Tapia, Nathaly Elizalde, Ivan Flores, Felipe M Rojas, Annelise Goecke, Loreto Cuitino, Cristhian A Urzua","doi":"10.3389/fimmu.2025.1584905","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1584905","url":null,"abstract":"<p><p>Uveitis, a group of heterogeneous diseases causing ocular inflammation, is a major contributor to vision loss globally. While systemic corticosteroids (CS) are the mainstay treatment, identifying CS-refractory patients remains a significant challenge. This study aimed to explore cytokine expression and Glucocorticoid Receptor (GR) levels as biomarkers for the early detection of CS-refractory cases in non-infectious uveitis. We assayed blood samples from 19 patients with non-infectious uveitis, for the expression of IL-6, IL-17A, TNF-α, IL-10 and GRα. The cohort included 11 refractory and 8 sensitive patients, categorized based on their clinical response to corticosteroids (prednisone 1 mg/kg/day). Blood draws were conducted at three time points (at baseline, day 7- and day 14 after CS initiation), and peripheral blood mononuclear cells (PBMCs) were isolated to measure cytokine and GRα transcript levels via real-time PCR. The expression levels of GRα and cytokines IL-6, IL-17A and TNF-α did not show significant changes between CS-sensitive and CS-refractory patients on the different days of treatment. However, IL-10 expression levels as the day14-to-day7 ratio were significantly higher in patients sensitive to CS therapy. A higher day14-to-day7 ratio was also found for the IL-6/IL-10, IL-17A/IL-10 and GRα/IL-10 ratios. ROC curve analysis demonstrated a robust predictive performance of IL-10 mRNA expression and the IL-6/IL-10 ratio for identifying CS-refractory patients. In conclusion, the expression of IL-10 and the IL-6/IL-10 ratio hold promise as early predictive biomarkers for CS treatment refractoriness in patients with non-infectious uveitis. These findings offer valuable insights into personalized treatment strategies, potentially leading to improved clinical outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1584905"},"PeriodicalIF":5.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157971","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}