Journal of Translational Medicine最新文献

{"title":"Engineering macrophages for targeted immunotherapy and drug delivery in melanoma.","authors":"Xudong Liu, Ye Liu, Danyu Zhao, Dehong Shan, Chenghao Guo, Lianqun Jia","doi":"10.1186/s12967-025-06687-w","DOIUrl":"10.1186/s12967-025-06687-w","url":null,"abstract":"<p><p>Melanoma is a highly aggressive skin cancer with a high metastatic potential and poor prognosis. While immune checkpoint inhibitors have revolutionized treatment, many patients remain unresponsive. Engineered macrophages have emerged as promising tools in immunotherapy and targeted drug delivery. This review explores three major strategies: cytokine engineering to enhance pro-inflammatory activity, chimeric antigen receptor (CAR)-modified macrophages for antigen-specific targeting, and macrophage-based platforms for nanoparticle-mediated drug delivery. Preclinical evidence supports their capacity to modulate the tumor microenvironment, enhance T cell recruitment, and reduce tumor growth. These strategies offer complementary approaches that may overcome resistance to current therapies. We also discuss current limitations and future directions, emphasizing the potential for clinical translation of these macrophage-based interventions.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"998"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137899","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":"Potential biomarkers of idiopathic pulmonary fibrosis: metabonomics driven lipid profiling.","authors":"Wenjie Cai, Haoyu Zhang, Zhouzhou Li, Mingyun Cai, Peng Chen, Na Guo, Xinyu Song","doi":"10.1186/s12967-025-06975-5","DOIUrl":"10.1186/s12967-025-06975-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. At present, the diagnosis of pulmonary fibrosis relies on high-resolution CT and invasive lung biopsy. In view of the lack of specific serum biomarkers in the diagnosis and monitoring of IPF, it is urgent to adopt an integrated metabolomics analysis strategy to screen and verify specific potential biomarkers, and to establish their translational value in the diagnosis, severity and prognosis of IPF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;In this study, an integrated metabolomics analysis strategy was used to screen and validate specific potential biomarkers for the diagnosis and evaluation of IPF severity and prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In this study, the serum metabolome of the two groups was compared by liquid chromatography-mass spectrometry (LC-MS) to study the characteristics of metabolic changes related to the disease (n = 30) and to screen potential biomarkers. Then multivariate regression analysis and correlation network modeling were used to analyze the correlation between target metabolites and pulmonary function parameters, hematological parameters and coagulation function parameters.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multiple pathways related to lipid metabolism were enriched in IPF patients compared to controls, including cholesterol metabolism, sphingolipid metabolism, steroid metabolism, and biosynthetic terpenoid metabolism. In addition, 37 compounds related to lipid metabolism were enriched in IPF patients, among which Palmitoyl ethanolamide (PEA) and 2-amino-1,3,4-octadecanetriol were significantly increased. ROC curve analysis, Kaplan-Meier application analysis model and multivariate Cox regression analysis showed that the two potential biomarkers could be used for the diagnosis and prognosis evaluation of IPF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study clarified that metabolic reprogramming and lipid metabolism disorder are significant characteristics of IPF. PEA and 2-Amino-1,3,4-octadecanetriol May be potential biomarkers for patients with IPF and have diagnostic and prognostic evaluation value for IPF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Highlights: &lt;/strong&gt;Through systematic metabolomics analysis, two novel serum lipid metabolites were identified as potential biomarkers for IPF for the first time. It has been confirmed that IPF patients exhibit significant reprogramming of lipid metabolism. It was the first time that 2-amino-1,3,4-octadecanetriol was reported to have a significant positive correlation with the abnormal coagulation function indicators (APTT, Fib, D-dimer) in patients with IPF. This provides a new metabolic perspective for understanding the pathophysiological mechanism of the increased risk of venous thromboembolism (VTE) in IPF patients. Both of the two potential biomarkers were negatively correlated with hemoglobin. This connects the often overlooked IPF complication of nutritional metabolism imbal","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1010"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137892","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":"Integrative single-cell and machine learning approach to characterize immunogenic cell death and tumor microenvironment in LUAD.","authors":"Han Zhang, Qiuqiao Mu, Yuhang Jiang, Xiaojiang Zhao, Xiaoteng Jia, Kai Wang, Xin Li, Daqiang Sun","doi":"10.1186/s12967-025-06889-2","DOIUrl":"10.1186/s12967-025-06889-2","url":null,"abstract":"<p><strong>Background: </strong>Immunogenic cell death (ICD) triggers antitumor immune responses and plays a critical role in shaping the tumor microenvironment (TME). However, its specific contribution to lung adenocarcinoma (LUAD) progression and immunotherapy response remains insufficiently explored.</p><p><strong>Method: </strong>We integrated single-cell RNA sequencing with machine learning to characterize ICD-related transcriptional features in LUAD. ICD activity was quantified across cell types using five scoring algorithms. To develop a robust prognostic model, we evaluated over 100 machine learning algorithm combinations and selected the CoxBoost + SuperPC approach based on the highest concordance index (C-index). The resulting ICD-related gene signature (ICDRS) was validated in six external cohorts. Downstream analyses included immune infiltration, mutation profiling, drug sensitivity, and immunotherapy response. SLC2A1 was selected for functional validation using qRT-PCR, CCK-8, Transwell, colony formation, and xenograft assays.</p><p><strong>Results: </strong>Single-cell analysis revealed that macrophages exhibited the highest ICD activity and contributed significantly to intercellular communication. Based on ICD-associated genes, the ICDRS model consisting of 11 core genes was constructed and showed superior prognostic performance over 112 published LUAD signatures across multiple cohorts. The ICDRS stratified patients into distinct risk groups with significant differences in overall survival, immune infiltration patterns, and immunotherapy benefit. Low-risk patients exhibited higher levels of CD8⁺ T cells, dendritic cells, and immune function scores, along with greater sensitivity to standard chemotherapeutics and immune checkpoint inhibitors. Functional experiments confirmed that SLC2A1 was upregulated in LUAD tissues and cell lines. Silencing SLC2A1 suppressed proliferation and invasion in vitro and inhibited tumor growth in xenograft models, supporting its oncogenic role.</p><p><strong>Conclusion: </strong>This study highlights the crucial role of ICD in LUAD immune regulation and prognosis. The ICDRS serves as a robust biomarker for risk stratification and immunotherapy guidance, while SLC2A1 emerges as a potential therapeutic target to augment immunotherapeutic efficacy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1000"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137841","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 role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.","authors":"Shengbiao Li, Mi Li, Yi Zhang, Ji Chen, Jiapan Li, Shubo Fu, Jingyan Yi, Rong Li, Gan Qiao, Yang Yu, Chunxiang Zhang, Qiuhong Li","doi":"10.1186/s12967-025-06890-9","DOIUrl":"10.1186/s12967-025-06890-9","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1007"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137975","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":"CCDC137 knockdown suppresses bladder cancer progression by downregulating SCD.","authors":"Haiyu Zhang, Weisheng Huang, Zhimao Cai, Shuanzhu Mou, Yuhan Liu, Bing Yan, Wendong Jiang, Yue Liu, Qiaolin Mei, Xinhui Liao, Yuchen Liu, Hongbing Mei","doi":"10.1186/s12967-025-07033-w","DOIUrl":"10.1186/s12967-025-07033-w","url":null,"abstract":"<p><strong>Background: </strong>The Coiled-coil domain-containing (CCDC) family, due to its unique protein structural domain and broad involvement in diverse biological processes, has emerged as a focus in oncology research. Nevertheless, its clinical significance and function in bladder cancer (BLCA) remain poorly defined.</p><p><strong>Methods: </strong>Machine learning algorithms were employed to identify pivotal CCDC genes in the cancer genome atlas (TCGA), and a prognostic model was subsequently constructed. Multi-omics data encompassing pan-cancer cohorts, single-cell sequencing, and spatial transcriptomics were integrated to characterize the expression patterns and prognostic significance of Coiled-coil domain-containing 137 (CCDC137), a previously uncharacterized CCDC family member in BLCA. Tissue microarray confirmed CCDC137 abnormal expression in bladder carcinoma specimens. The effect of CCDC137 knockdown on BLCA progression was evaluated through CCK8 assay, clonogenic formation, wound healing, Transwell, and subcutaneous xenograft models. RNA sequencing, quantitative RT-PCR, and western blot were utilized to delineate its regulatory network.</p><p><strong>Results: </strong>A prognostic model incorporating 10 CCDC genes was successfully established in the TCGA-BLCA cohort. Then, we found that CCDC137 exhibited pan-cancer overexpression and usually correlation with poor clinical outcomes. Immunohistochemistry further substantiated its dysregulation in bladder carcinoma. Integrated multi-omics analyses suggested associations between CCDC137 expression and a tumor immunosuppressive microenvironment. CCDC137 knockdown significantly suppressed bladder cancer cell proliferation and migratory capacity in vitro. Correspondingly, subcutaneous xenograft tumor growth was inhibited in vivo. Moreover, decreased expression of stearoyl-CoA desaturase (SCD), a key lipid metabolic enzyme, accompanied CCDC137 depletion. These findings collectively suggest a cancer-promoting role for CCDC137 in bladder carcinoma.</p><p><strong>Conclusions: </strong>This systematic investigation combining multi-omics bioinformatics analyses and experimental validation demonstrates the role of CCDC137 in bladder carcinoma progression, providing novel mechanistic insights into the pathogenesis of BLCA and offering a theoretical foundation for therapeutic targeting of CCDC137 in urothelial malignancies.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1013"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137873","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":"SH3BP5-driven metabolic-immune crosstalk in DLBCL: a prognostic biomarker and therapeutic target for reshaping immunosuppressive microenvironment.","authors":"Tong Wu, Yi Yang, Yuan Zong, Jiawen Zhao, Xiaoyu Zhao, Lei Li, Yiming Gao, Ning Li, Liting Jiang, Yinyin Xie","doi":"10.1186/s12967-025-06951-z","DOIUrl":"10.1186/s12967-025-06951-z","url":null,"abstract":"<p><strong>Background: </strong>Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous and aggressive hematologic malignancy, with the activated B-cell-like (ABC) subtype displaying particularly poor prognosis due to inherent treatment resistance and elevated recurrence rates. Despite advances in targeted therapies and immunotherapies, a significant proportion of patients experience relapse or refractory disease, highlighting the urgent need for novel biomarkers and innovative therapeutic strategies to improve clinical outcomes.</p><p><strong>Methods: </strong>A multi-dimensional analysis of SH3BP5 expression was performed across DLBCL subtypes, integrating transcriptomic, proteomic, and clinical datasets to assess its correlation with immune infiltration, tumor metabolism, and patient prognosis. Single-cell RNA sequencing data were employed to examine the tumor microenvironment (TME) with higher resolution. Further analysis of the association between SH3BP5 and immune checkpoint gene expression was conducted to explore its potential role in immunotherapy response. Functional in vitro assays were carried out to assess the impact of SH3BP5 knockdown on DLBCL cell proliferation and apoptosis.</p><p><strong>Results: </strong>The analysis revealed that SH3BP5 is preferentially overexpressed in the ABC subtype of DLBCL across multiple datasets and validated cohorts, and its high expression is significantly associated with poor overall survival. Single-cell transcriptomic profiling demonstrated that SH3BP5 is mainly expressed in malignant B cells and inversely correlated with immune cell infiltration, particularly CD8 + T cells. Mechanistically, pathway enrichment and metabolic assays indicated that SH3BP5 is linked to mitochondrial metabolic reprogramming, promoting oxidative phosphorylation (OXPHOS) and potentially contributing to reduced responsiveness to immune checkpoint inhibitors (ICIs). Functional studies showed that SH3BP5 knockdown significantly suppressed DLBCL cell proliferation, induced apoptosis, and reduced tumor cell viability in vitro.</p><p><strong>Conclusion: </strong>This study suggests that SH3BP5 may serve as a prognostic biomarker and a potential therapeutic target in DLBCL, particularly within the ABC subtype. By delineating its associations with immune evasion and metabolic reprogramming, these findings provide a mechanistic basis for further exploration of SH3BP5-targeted interventions to help overcome therapy resistance. Future studies in larger clinical cohorts and functional models are warranted to validate these results and assess the potential of integrating SH3BP5 expression profiling into precision medicine strategies for DLBCL.</p><p><strong>Trial registration: </strong>The study was registered in the Chinese Clinical Trial Registry (ChiCTR2200060430; http://www.chictr.org.cn/ ) on June 1, 2022.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1003"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137812","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":"Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.","authors":"Amalia Luce, Marco Bocchetti, Alessia Maria Cossu, Madhura S Tathode, David J Boocock, Clare Coveney, Maria Preziosa Romano, Maria Roberta De Iesu, Ines Simeone, Luigi Mele, Giovanni Vitale, Rossella Sperlongano, Gabriella Misso, Elisabetta A M Verderio, Silvia Zappavigna, Michele Caraglia","doi":"10.1186/s12967-025-07039-4","DOIUrl":"10.1186/s12967-025-07039-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p enhances anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. Here, we investigated the molecular mechanisms underlying miR-423-5p function through a comprehensive proteomic approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We generated an HCC cell line stably overexpressing miR-423-5p via lentiviral transduction. Total proteins were extracted from SNU-387 cells, enzymatically digested into peptides, and subsequently analysed by liquid chromatography-tandem mass spectrometry (LC-MS/M). Raw spectral data were processed and quantified using MaxQuant. Differentially expressed proteins (DEPs) were defined based on fold-change (|log2FC| ≥ 1) and false discovery rate (FDR &lt; 0.05). The full proteomic dataset is available via the ProteomeXchange repository (identifier: PXD064869). Functional enrichment analysis of DEPs were performed using DAVID and Reactome. To assess clinical relevance, predicted and validated miR-423-5p targets were integrated with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset using GEPIA platform. Survival analyses were performed using the Kaplan-Meier method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Proteomic profiling identified 698 DEPs in miR-423-5p-overexpressing cells compared to controls with significant enrichment in metabolic pathways, related to purine/pyrimidine metabolism and gluconeogenesis. Integration with bioinformatic predictions and miRTarBase validation identified 43 DEPs as potential direct targets of miR-423-5p. Among these, seven proteins (ACACA, ANKRD52, DVL3, MCM5, MCM7, RRM2, SPNS1, and SRM) were significantly associated with patient prognosis in the TCGA-LIHC cohort. These targets were downregulated in miR-423-5p-overexpressing cells but upregulated in advanced-stage HCC tissues, suggesting a potential role for miR-423-5p in the regulation of HCC pathogenesis. Stage-specific expression analysis showed increased levels from stage I to III, followed by a decline at stage IV. Notably, we experimentally confirmed miR-423-5p-mediated suppression of MCM7, DVL3, IMPDH1, and SRM (SPEE), supporting their functional involvement in HCC progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, our findings support a tumour-suppressive role for miR-423-5p in HCC, mediated by modulation of metabolic pathways and suppression of oncogenic proteins. These results suggest that miR-423-5p and its downstream effectors may serve as promising biomarkers and potential therapeutic targets in HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Highlights: &lt;/strong&gt;miR-423-5p acts as a tumor suppressor in HCC by targeting key nodes of pro-tumorigenic signalling. miR-423-5p significantly altered metabolic pathways, including purine/pyrimidine","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1008"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137859","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":"Spatiotemporal microenvironment landscape and malignant epithelial pattern transition in breast ductal carcinoma progression.","authors":"Xifu Cheng, Wenjuan Zeng, Bingzhe Yin, Jiawei Gui, Hengbin Zhang, Zhenxing Lv, Simin Zhang, Yao Zhou","doi":"10.1186/s12967-025-07010-3","DOIUrl":"10.1186/s12967-025-07010-3","url":null,"abstract":"<p><strong>Background: </strong>Owing to the complexity of TME components and the heterogeneity of cancer cells, the relationship between the niches of TME and prognosis in breast ductal carcinoma remains unknown. The staged characteristics of corresponding cancer cell behaviors are unclear. Our study aims to reveal spatial structures and specific cellular information of TME and cancer cells subgroups during the progression from DCIS to IDC and lymph node metastasis.</p><p><strong>Methods: </strong>Single-cell sequencing, spatial transcriptomics, bulk RNA sequencing datasets were used to explore the changes in microenvironmental components and transcriptional programs of tumor cells during the progression of breast ductal carcinoma. Immunohistochemistry, multiplex immunofluorescence, flow cytometry cell cycle detection, invasion migration experiments, and WB imprinting were employed for validation.</p><p><strong>Results: </strong>Analysis of TME cell type subsets revealed the accumulation of T_EX, iTreg, and stress-phenotype TAM in the mammary gland in situ during the invasion process. Lymphatic metastases exhibited enrichment of nTregs and a more naïve-like CD8 T cell population. Spatial analysis and survival analysis showed that the spatial niches of CD4 T_N and phagocytic-phenotype macrophages were associated with a favorable prognosis, and these niches were lost during disease progression. The proliferative subpopulation of breast ductal carcinoma was enriched in lymphatic metastatic tissues, expressing high levels of FAM111B and exhibiting intense TCA and oxidative phosphorylation metabolism. Silencing FAM111B led to cell cycle arrest, decreased invasion and migration abilities, and downregulation of core mediator genes for cuproptosis and disulfidptosis.</p><p><strong>Conclusions: </strong>The stage-specific microenvironmental characteristics of breast ductal carcinoma correspond to some extent to the behavior of tumor cells. During the progression of ductal carcinoma in breast tissue, the establishment of an immunosuppressive microenvironment occurs. The microenvironmental spectrum at lymph node metastases differs somewhat, corresponding to a more enriched turnover of cancer cell proliferation and death. Inhibitors of FAM111B and inducers of cuproptosis and disulfidptosis may serve as potential therapeutic targets for proliferative subgroups.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"996"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137918","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":"Inhibition of DDR1 potentiates carbon ion radiotherapy by promoting ferroptosis and immunogenic death in head and neck squamous cell carcinoma.","authors":"Wei Hu, Qingting Huang, Li Chen, Shikai Geng, Haojiong Zhang, Huaiyuan Chen, Xingyu Liu, Jingqin Zhong, Fengtao Su, Chunlin Shao, Lin Kong","doi":"10.1186/s12967-025-07062-5","DOIUrl":"10.1186/s12967-025-07062-5","url":null,"abstract":"<p><strong>Background: </strong>Carbon ion radiotherapy (CIR) has emerged as a promising therapeutic modality for photon-resistant malignancies due to its unique physical depth-dose distribution and enhanced radiobiological effectiveness. Nevertheless, treatment resistance persists in certain recurrent or refractory head and neck squamous cell carcinoma (HNSCC) cases, underscoring the need for novel combinatorial strategies. Here, we demonstrated the sensitizing effect of targeting discoidin domain receptor 1 (DDR1) in HNSCC for CIR.</p><p><strong>Methods: </strong>MOC1 and and Cal27 cell lines along with tumor-bearing C57BL/6 mice were used for in vitro and in vivo studies. DDR1 was knocked down via lentivirus. Cell viability and proliferation were assessed by CCK-8 and colony formation assays. Immunogenicity and tumor-infiltrating lymphocytes were measured via flow cytometry and immunofluorescence. Tumor suppression mechanisms were investigated using RNA sequencing and bioinformatics. Ferroptosis markers (lipid peroxidation, iron, ROS) were detected using MDA, BODIPY 581/591 C11, FerroOrange, and DCFH-DA probes. Upstream ferroptosis mechanisms were analyzed by Western blot, co-immunoprecipitation, key molecule modulator administration, and SCD1 overexpression.</p><p><strong>Results: </strong>We demonstrated that targeting DDR1 potentiated CIR by triggering ferroptosis-mediated immunogenic cell death, which in turn enhanced antitumor immunity. Mechanistically, DDR1 sustained tumor cell survival by forming 14-3-3-mediated assembly of a DDR1/14-3-3/Akt ternary complex, thereby activating the Akt/mTORC1/SREBP1/SCD1 axis to promote monounsaturated fatty acid (MUFA) biosynthesis and suppress ferroptosis. Silencing DDR1 disrupted this complex, alleviating MUFA-mediated ferroptosis inhibition and subsequently increasing tumor immunogenicity. This immunogenic shift facilitated CD8 + T cell infiltration and cytotoxicity, amplifying CIR-induced tumor suppression. Furthermore, pharmacological inhibition of DDR1 using the small-molecule inhibitor 7rh recapitulated these effects, demonstrating potent anti-proliferative and ferroptosis-inducing capabilities, enhancing CIR sensitivity to better control tumor progression.</p><p><strong>Conclusions: </strong>Our findings positioned DDR1 targeting as a therapeutic strategy to potentiate CIR through immunogenic ferroptosis induction in HNSCC.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1011"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137848","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 dual-branch deep learning network for circulating tumor cells classification.","authors":"Chao Han, Jiaquan Lin, Yanfang Liang, Cong Li, Danni Wang, Gonghua Huang, Ruoxi Hong, Jincheng Zeng","doi":"10.1186/s12967-025-07057-2","DOIUrl":"10.1186/s12967-025-07057-2","url":null,"abstract":"<p><strong>Background: </strong>Circulating tumor cells (CTCs) in peripheral blood are crucial for prognosis, treatment response, disease monitoring, and personalized therapy. However, identifying CTCs remains challenging due to their scarcity and heterogeneity, even with advanced deep learning models.</p><p><strong>Methods: </strong>This study introduces an innovative hybrid framework combining a dual-branch network with traditional image processing techniques and automated CTC identification. By incorporating image and fluorescence attributes, the framework enhances feature representation robustness. Performance was evaluated using accuracy, precision, and recall metrics and comparisons with pathologists' manual counting.</p><p><strong>Results: </strong>The framework achieved 97.05% accuracy in distinguishing CTCs from non-CTCs, with performance closely matching pathologists' manual counting in survival prediction. The dual-branch network improved efficiency by leveraging segmentation algorithms, surpassing conventional methods. Clinical trials confirmed its practicality for direct clinical use.</p><p><strong>Conclusions: </strong>The proposed framework enhances CTC identification accuracy and efficiency, demonstrating strong clinical applicability. Its output results can be directly utilized for prognosis without manual intervention, offering significant potential for personalized therapy.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"1002"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137891","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}