Journal of Translational Medicine最新文献

{"title":"Cyclosporine A promotes renal fibrosis through activating endoplasmic reticulum stress by targeting miR-212-5p/ATF6 axis.","authors":"Juan Wang, Zheng Li, Bei Qing, Zhenkun Xia, Yunchang Yuan, Lei Zhang, Zhiwen Liu","doi":"10.1186/s12967-026-08252-5","DOIUrl":"https://doi.org/10.1186/s12967-026-08252-5","url":null,"abstract":"<p><strong>Introduction: </strong>Cyclosporine A (CsA) is a widely used immunosuppressive drug, but its long-term use is associated with renal fibrosis. Despite its clinical importance, the molecular mechanisms underlying CsA-induced renal fibrosis remain poorly understood.</p><p><strong>Methods: </strong>We used C57BL/6 mice (n = 6 per group) treated with CsA (30 mg/kg/day, gavage) and Boston University mouse proximal tubular (BUMPT) cells (n = 6 per group) exposed to CsA (8 µM). Assessments included Masson's trichrome staining, Western blot, quantitative real-time PCR, immunohistochemistry, and in situ hybridization. Mechanistic studies employed miR-212-5p mimics and inhibitors, activating transcription factor 6 (ATF6) overexpression, and the endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid (4-PBA). Data are presented as mean ± standard deviation; statistical significance was defined as p < 0.05.</p><p><strong>Results: </strong>CsA induced significant renal fibrosis in vivo and in vitro, evidenced by increased collagen deposition and elevated expression of alpha-smooth muscle actin (α-SMA), fibronectin, collagen type I and IV, and key profibrotic factors (p < 0.05). RNA analysis revealed that miR-212-5p was markedly upregulated in CsA-treated kidneys, predominantly in renal tubules. Concurrently, ATF6, a protective component of the unfolded protein response (UPR), was significantly downregulated. Bioinformatics prediction and luciferase reporter assays confirmed that miR-212-5p directly targets the 3' untranslated region of Atf6 mRNA. Functionally, miR-212-5p mimic exacerbated CsA-induced ATF6 suppression and fibrosis, whereas anti-miR-212-5p restored ATF6 expression, attenuated ER stress, and significantly reduced fibrotic markers. Similarly, ATF6 overexpression or ER stress inhibition with 4-PBA ameliorated CsA-induced fibrosis.</p><p><strong>Conclusions: </strong>Our findings position miR-212-5p as a previously unrecognized molecular target of CsA and establish the miR-212-5p/ATF6 axis as a central driver of CsA-induced nephrotoxicity. The findings provide new insights into the molecular mechanisms of CsA nephrotoxicity and identify a potential therapeutic target for preventing CsA-induced renal fibrosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the Mediterranean diet on oxidative stress: a systematic review and meta-analysis of randomized clinical trials.","authors":"Hongya Du, Yi Feng, Ruixi Zhou, Yupeng Lei, Bixin Deng, Tiechao Ruan, Wenting Lu, Dezhi Mu","doi":"10.1186/s12967-026-08233-8","DOIUrl":"https://doi.org/10.1186/s12967-026-08233-8","url":null,"abstract":"<p><strong>Background: </strong>The Mediterranean diet (MD) is rich in antioxidant components that can increase the antioxidant capacity of the body and improve the oxidative stress status. This systematic review and meta-analysis aimed to determine the ability of the MD to regulate oxidative stress status.</p><p><strong>Methods: </strong>This study was conducted in accordance with the PRISMA guidelines. The PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials, and Chinese Clinical Trial databases were searched from their inception to November 2024. Randomized controlled trials that investigated the relationship between MD patterns and oxidative stress biomarkers were selected to assess the impact of the MD on oxidative stress markers.</p><p><strong>Results: </strong>The 20 studies included in the analysis encompassed 2,208 participants and examined 13 indicators. The MD increased the total blood antioxidant capacity (standardized mean difference [SMD]: 0.57, 95% confidence interval [CI]: 0.31 to 0.83; p < 0.001), decreased urine F2-isoprostanes (SMD: -0.40, 95% CI: -0.67 to -0.12; p = 0.005), and significantly decreased blood malondialdehyde levels (SMD: -0.70, 95% CI: -1.12 to -0.27; p = 0.001).</p><p><strong>Conclusion: </strong>These findings suggest that the MD can enhance the body's antioxidant capacity and improve lipid peroxidation. Therefore, an MD may be an effective method for reducing oxidative stress.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Super-enhancer-driven LncRNA MIR205HG promotes esophageal squamous cell carcinoma progression via glycolysis reprogramming.","authors":"Ze-Jun Zheng, Yin-Qiao Liu, Yan-Shang Li, Dong-Chen Han, Jun-De Zhu, Qi-Xin Su, Zhi-Ya Wang, Chun Li, Zhuo-Ying Kang, Jin-Cheng Guo, Ying-Hua Xie, Jing-Ru Ye, Lu-Shuang Mao, Jiang-Yun Peng, Xing-Dong Xiong, Jian-Jun Xie","doi":"10.1186/s12967-026-08202-1","DOIUrl":"https://doi.org/10.1186/s12967-026-08202-1","url":null,"abstract":"<p><strong>Background: </strong>Super-enhancer-associated long non-coding RNAs (lncRNAs) have been shown to play key roles in the occurrence and development of malignant tumors, including esophageal squamous cell carcinoma (ESCC), yet their precise molecular mechanisms remain elusive.</p><p><strong>Methods: </strong>ChIP-Seq, dual-luciferase reporter assays, HiChIP-Seq, and ChIP-qPCR were performed to investigate the transcriptional regulation mechanism of MIR205HG. The functions and downstream signal transduction mechanisms of MIR205HG in ESCC were explored by a series of in vitro and in vivo assays. Furthermore, comprehensive bioinformatics methods were used to analyze its correlation with ESCC patient survival.</p><p><strong>Results: </strong>Here, we identified and characterized MIR205HG, a lncRNA driven by super-enhancer, as a crucial oncogene in ESCC. MIR205HG was up-regulated in SCCs and its high expression correlated with poor clinical outcomes. Both TP63 and KLF5, two important master transcription factors in ESCC, could simultaneously occupy the super-enhancer region at the MIR205HG locus to promote its transcription and overexpression. MIR205HG is essential for ESCC proliferation, migration, invasion, and the growth of xenograft tumors in vitro and in vivo. Mechanistically, MIR205HG directly bound PTBP3 and acted as a molecular scaffold to promote HIF-1α translation, leading to enhanced cellular glycolysis via up-regulating the expression of HK2 and LDHA. Moreover, survival and pseudotime analyses of ESCC scRNA-seq data revealed a significant positive correlation between MIR205HG/PTBP3 signaling and the stemness and malignancy of ESCC cells. Finally, we showed that specifically targeting MIR205HG-SE using a CRISPR interference method resulted in potent suppressive effects on ESCC malignant phenotypes.</p><p><strong>Conclusion: </strong>We identified a pivotal oncogenic super-enhancer-driven lncRNA, MIR205HG, which interacts with PTBP3 to promote glycolysis in ESCC. It may serve as a promising prognostic biomarker and therapeutic target for patients.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-reactive tissue-resident memory T lymphocytes-concepts, evidence, and open questions.","authors":"Hong Lei, Ying Sun, Weihua Gong, Jun Dong","doi":"10.1186/s12967-026-08137-7","DOIUrl":"https://doi.org/10.1186/s12967-026-08137-7","url":null,"abstract":"<p><strong>Background: </strong>Tissue-resident memory T (Trm) cells have emerged as a distinct lymphocyte lineage that provides rapid, frontline immune surveillance in peripheral tissues while also contributing to durable systemic immunity. A critical and evolving aspect of Trm cell biology is their inherent cross-reactivity-the ability of a single T cell receptor (TCR) to recognize and respond to multiple related or unrelated antigens beyond its primary target.</p><p><strong>Main body: </strong>This review synthesizes current knowledge on the dual roles of cross-reactive Trm cells, which can mediate broad protection against heterologous infections and cancers but may also precipitate or exacerbate autoimmune pathology. We first address the developmental origins, tissue-specific distribution (from barrier surfaces to internal organs, including the central nervous system and bone marrow niches), and key functions that define the Trm population. A central focus is placed on the mechanistic basis of TCR cross-reactivity, comparing and contrasting its regulation in circulating memory T cells versus Trm cells. We delve into how tissue-specific signals, particularly local cytokine milieus and epigenetic reprogramming such as demethylation imprints, shape the functional avidity and antigenic breadth of Trm cell responses. Finally, we discuss emerging therapeutic strategies designed to either harness the protective cross-reactivity of Trm cells for next-generation vaccines and immunotherapies or to restrain its detrimental potential in autoimmune and inflammatory diseases.</p><p><strong>Conclusions: </strong>Trm cells are powerful immune sentinels whose TCR cross-reactivity enables broad protection but also risks autoimmunity. Understanding these precise rules is key to developing Trm-based immunotherapies against cancer and infections while avoiding autoimmunity.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell profiling uncovers a hypoxia-vascular-immune axis underlying poor immunotherapy response in acral versus cutaneous melanoma.","authors":"Qian Dong, Yiming Zhang, Fuchu He, Aihua Sun","doi":"10.1186/s12967-026-08201-2","DOIUrl":"https://doi.org/10.1186/s12967-026-08201-2","url":null,"abstract":"<p><strong>Background: </strong>Acral melanoma (AM), accounting for ~50% of melanomas in Asian populations, exhibits far poorer immunotherapy response (anti-PD-1 ORR < 20%) than cutaneous melanoma (CM, ~43.7%). While the tumor microenvironment (TME) plays a pivotal role in immunotherapy resistance, previous studies mainly focused on immune cells, neglecting stromal components like pericytes-creating a critical knowledge gap in understanding AM's therapeutic refractoriness.</p><p><strong>Methods: </strong>We integrated multiple single-cell transcriptomic datasets from 31 acral melanoma, 13 cutaneous melanoma and 35 normal skin samples. Comprehensive bioinformatics analyses including cell type annotation, differential expression, gene functional enrichment, and cell-cell interaction analysis, were performed to delineate the tumor microenvironment differences between acral and cutaneous melanoma. Key findings were validated using spatial transcriptomics, bulk RNA-seq datasets, and functional assays including qPCR and western blot.</p><p><strong>Results: </strong>AM had a more immunosuppressive TME, enriched in collagen-secreting RGS5⁺/COL3A1⁺ pericytes that co-localized with KDR⁺/PODXL⁺ endothelial cells, associated with vascular abnormalities and hypoxia. These collagen-secreting RGS5⁺/COL3A1⁺ pericytes (enriched in AM) were significantly negatively correlated with the infiltration ratio of CD8⁺ tumor-infiltrating lymphocytes (TILs); moreover, in immunotherapy cohorts, high expression of the collagen-secreting pericyte marker RGS5 was associated with poorer response to immune checkpoint blockade (ICB) treatment. We also identified a hypoxia-related NECTIN2-TIGIT immunosuppressive axis: hypoxia upregulated NECTIN2 on multiple cells, interacting with TIGIT on T cells to potentially exacerbate dysfunction.</p><p><strong>Conclusions: </strong>This study provides insights into vascular-stromal features associated with immunotherapy resistance in AM, highlighting RGS5⁺/COL3A1⁺ pericytes and the NECTIN2-TIGIT axis as targets, and guides development of effective combination immunotherapies for AM.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intratumoral microbiota promote pancreatic cancer progression via NaAc-mediated activation of the GPR43/AMPK/HADH pathway.","authors":"Zhou Chen, Dacheng Jin, Hu Wang, Qizhou Bai, Yan Wang, Yunjiu Gou","doi":"10.1186/s12967-026-08231-w","DOIUrl":"https://doi.org/10.1186/s12967-026-08231-w","url":null,"abstract":"<p><strong>Background: </strong>Intratumoral microbiota are essential components of tumours and are substantially involved in tumour initiation, progression, and treatment. However, owing to the vast diversity and abundance of microbial species, understanding their molecular mechanisms within tumours, particularly in pancreatic cancer (PC), remains challenging.</p><p><strong>Methods: </strong>Microbiota composition was analysed in pancreatic cystic neoplasm (PCN) and pancreatic ductal adenocarcinoma (PDAC) tissues using 16S rRNA sequencing. Liquid chromatography-mass spectrometry (LC-MS) was employed in the same samples to quantify tissue metabolites. Subsequently, the association between intratumoral microbiota and metabolites was examined to investigate potential interactions. Western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry were used to detect the expression of 3-hydroxyacyl-CoA dehydrogenase (HADH), AMP-activated protein kinase (AMPK), and G protein-coupled receptor 43 (GPR43). The biological role of the intratumoral bacterial metabolite sodium acetate (NaAc) was determined through in vitro and in vivo experiments.</p><p><strong>Results: </strong>Certain bacterial taxa, including Muribaculaceae, Prevotella, Lachnospiraceae NK4A136 group, and Blautia, were significantly enriched in PDAC tissues and were associated with lipid molecules. Specific taxa exhibited positive correlations with lipid molecules in PDAC tissues. Low concentrations of NaAc promoted PC cell proliferation and migration in vitro and enhanced tumour growth in vivo. Mechanistically, NaAc activated the GPR43/AMPK/HADH signalling pathway in PC cells, leading to increased fatty acid oxidation.</p><p><strong>Conclusions: </strong>Specific intratumoral microbiota contribute to the progression from PCN and PDAC by modulating lipid metabolism. These findings provide a theoretical framework for understanding the microbiota-driven mechanisms in PDAC and highlight their role in tumour growth.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B7-H3 interaction with cMet enhances lipolysis to drive malignant progression of glioma via pSTAT3-ATGL axis.","authors":"Xiaohan Hu, Liuqing Zhang, Yuepeng Li, Jianwei Wang, Wanqing Qi, Jingnan An, Xiaowei Li, Yuan Yang, Zhen Weng, Fang Li, Yunyun Xu","doi":"10.1186/s12967-026-08151-9","DOIUrl":"https://doi.org/10.1186/s12967-026-08151-9","url":null,"abstract":"<p><strong>Background: </strong>Although metabolic dysregulation serves as a pivotal hallmark in glioma, the detailed information about the lipid metabolism regulation is largely unknown. In the context of this investigation, we have identified B7-H3 - an immune checkpoint molecule of the B7 family - as a regulator of lipid metabolism in glioma.</p><p><strong>Methods: </strong>A series of enrichment analyses were applied to explore the interaction between metabolic reprogramming and prognosis in glioma. The expression and prognostic value of B7-H3 were detected in both public databases and clinical samples. Furthermore, the effect of B7-H3 on Glioma cells malignance and lipid metabolism was evaluated through in vivo and in vitro functional experiments. Finally, the molecular mechanism of B7-H3 was investigated by the study of transcriptome sequencing and key interacting proteins.</p><p><strong>Results: </strong>The metabolism associated genes (MAG) were firstly screened from the prognosis related differentially expressed genes (DEG) using the TCGA and verified CGGA derived primary and recurrent cohorts of glioma patients, and the immune checkpoint molecule CD276 (B7-H3) was selected due its significant poor prognosis correlation in both primary and recurrent glioma. Furthermore, both RNA sequencing and untargeted metabolomics profiling confirmed a strong correlation between B7-H3 and lipid metabolism in glioma. Notably, B7-H3 showed a significant positive correlation with lipolytic enzyme ATGL (PNPLA2) according to the above transcriptomic data and CGGA database of glioma. However, the receptors of B7-H3 on cancer cells remained poorly understood. Here, we reported that B7-H3 modulated abnormal lipolysis during glioma progression by forming a complex with cMet, and subsequent simultaneous promoting the phosphorylation of STAT3 and expression of ATGL. More importantly, B7-H3 protein level was associated with poor prognosis and correlated with ATGL status in glioma.</p><p><strong>Conclusions: </strong>Our results define B7-H3 as a lipolysis related factor that acts by driving glioma malignancy via the cMet-pSTAT3-ATGL pathway, thereby nominating both B7-H3 and ATGL as potential therapeutic targets for glioma.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGFBP in tumor immunity: a novel target for cancer immunotherapy.","authors":"Qingqiang Lei, Liangbin Lin, Hui Yu","doi":"10.1186/s12967-026-08204-z","DOIUrl":"https://doi.org/10.1186/s12967-026-08204-z","url":null,"abstract":"<p><strong>Background: </strong>The insulin-like growth factor-binding protein (IGFBP) family consists of soluble bioactive molecules that, together with insulin-like growth factors (IGFs) and their receptors, are critical modulators of endocrine, metabolic, and immune functions. IGFBPs serve as signaling intermediaries in fundamental cellular processes such as migration, differentiation, proliferation, and apoptosis. Although their role in immune regulation is well-documented, this understanding has not yet led to significant clinical progress, particularly in research utilizing human specimens.</p><p><strong>Main body: </strong>This review synthesizes current knowledge on the functions and mechanisms of IGFBPs within immune regulation and tumor immunology, highlighting their therapeutic potential. We specifically examine how IGFBPs influence diverse cell populations residing in the tumor immune microenvironment, primarily through IGF-dependent and IGF-independent pathways. The article highlights future research directions and potential targets for novel immunotherapy strategies. This article also synthesizes the latest clinical research data on the correlation between IGFBP expression levels and patient prognosis across various cancer types, strengthening the translational potential of IGFBPs as targets for immunotherapy.</p><p><strong>Conclusion: </strong>By detailing the impact of IGFBPs on the tumor immune landscape, we position this protein family as promising targets for the development of novel cancer immunotherapies.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon lambda in anti-viral defense and cancer: dual roles, mechanism and therapeutic potential.","authors":"Juliane Blümke, Barbara Seliger","doi":"10.1186/s12967-026-08209-8","DOIUrl":"https://doi.org/10.1186/s12967-026-08209-8","url":null,"abstract":"<p><strong>Background: </strong>The type III interferon family, known as interferon lambda (IFN-λ), consists of four isoforms (IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4) and plays essential roles in immune responses. It mediates anti-viral and anti-tumoral activities and is distinguished from type I and type II interferons (IFNs) by its interaction with a unique receptor complex involving IFN-λR1 and IL-10 Rβ predominantly expressed on epithelial cells and selected immune cell populations. This interaction results in activation of the JAK-STAT signaling pathway and transcription of interferon-stimulated genes (ISGs).</p><p><strong>Main body: </strong>IFN-λs exert anti-viral activities, particularly at epithelial and barrier surfaces, and have emerged as therapeutic agents for chronic viral infections like hepatitis C virus and influenza, providing an alternative to traditional IFN therapies with a more favorable safety profile. Beyond these anti-viral properties, IFN-λs contribute to tumor control by enhancing immune surveillance and modulating the composition of the tumor microenvironment. However, accumulating evidence indicates that IFN-λ cells may also exhibit pro-tumorigenic potential by promoting immune evasion and tumor progression in certain contexts. These opposing functions underscore the complexity of IFN-λ biology and the need for further research to elucidate the mechanisms governing its actions, identify biomarkers that predict IFN response and to develop targeted strategies that maximize its therapeutic benefits, while minimizing adverse effects.</p><p><strong>Conclusion: </strong>By elucidating the complex interplay between IFN-λ and the immune system, this review provides insights into its dual functions in immune-related diseases, its potential as a biomarker for disease monitoring and prediction of therapy response, and its potential for the development of targeted therapies in cancer treatment and viral infections. However, to improve the patients' outcomes in infectious diseases and cancer management, a comprehensive understanding of its context-specific effects is required to optimize its clinical application.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling metastasis and predicting drug response with malignant effusion-derived organoids: a systematic review and quantitative assessment.","authors":"Jingyu Peng, Shuting Tian, Li Liu, Yifang Deng","doi":"10.1186/s12967-026-08107-z","DOIUrl":"10.1186/s12967-026-08107-z","url":null,"abstract":"<p><strong>Background: </strong>Malignant effusions provide a critical window into metastatic biology. Malignant effusion-derived organoids (ME-PDTOs) hold promise for modeling metastasis and predicting drug response, but the evidence remains fragmented. This systematic review aims to synthesize current evidence on the validity of ME-PDTOs as metastasis models and their concordance with clinical drug responses.</p><p><strong>Methods: </strong>We systematically reviewed literature from the past 15 years in strict accordance with PRISMA 2020 guidelines for study identification and selection. Data on genetic, transcriptional, functional, and clinical correlation were extracted. Given sample size limitations and heterogeneity, a descriptive, study-level analysis was performed. Predictive performance (sensitivity, specificity) was calculated with 95% confidence intervals using multiple methods.</p><p><strong>Results: </strong>Sixteen studies (87 ME-PDTOs from 84 patients) were included. ME-PDTOs retained key driver mutations and displayed transcriptomic enrichment of epithelial-mesenchymal transition and stemness pathways. Functionally, they demonstrated migratory, invasive, and in vivo metastatic capacity. For drug response, six studies provided 77 drug-patient pairs (predominantly lung cancer, 89.6%). In the two largest lung cancer studies, ME-PDTO sensitivity for predicting clinical efficacy ranged from 0.82 to 0.90, and specificity from 0.80 to 1.00, though confidence intervals were wide in smaller studies.</p><p><strong>Conclusion: </strong>Current evidence suggests that ME-PDTOs can recapitulate key metastatic features and show a promising correlative trend with clinical drug responses in lung cancer. However, significant limitations exist: evidence is limited, heterogeneous, and subject to selection and measurement biases. Future standardized, prospective studies are needed to validate their clinical predictive utility and address translational challenges.</p><p><strong>Trial registration registration number (prospero): </strong>CRD420251107909.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"24 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839633","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}