Journal of Translational Medicine最新文献

{"title":"CHI3L1: a key driver in gastritis-to-cancer transformation.","authors":"Tao Li, Huizhong Jiang, Yucheng Gong, Mengting Liao, Yuanping Jia, Jiena Chen, Ming Dai, Yinan Yan, Xinyu Lu, Runhua Chen, Yuan Li, Yan Chen, Jie Lin, Yicong Li, Xia Ding","doi":"10.1186/s12967-025-06352-2","DOIUrl":"10.1186/s12967-025-06352-2","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer, recognized as one of the most lethal malignancies globally, progresses through a complex, multi-stage development. Elucidating the pathogenic mechanisms behind gastric carcinogenesis and identifying early diagnostic biomarkers are pivotal for decreasing the prevalence of gastric cancer.</p><p><strong>Methods: </strong>Using datasets on gastric cancer and its transformation from gastritis, we employed machine learning to create an early diagnostic model, identifying key genes and evaluating accuracy. We prioritized genes in the gastritis-to-cancer progression, identifying a central driver gene. Pathway analysis revealed its transformation role. Tissue microarrays and rat models validated the driver genes and networks, confirmed in cell and organoid models. We also identified cell types secreting CHI3L1 using single-cell RNA sequencing and multiplex immunohistochemistry, exploring their prognostic significance.</p><p><strong>Results: </strong>We identified 12 driver genes potentially involved in the gastritis-to-cancer transformation, with CHI3L1, MMP12, CXCL6, IDO1, and CCL20 emerging as the top five genes via a early gastric cancer diagnostic model. CHI3L1 was pinpointed as the central driver across the gastritis-to-cancer spectrum, with its upregulation, along with CD44, β-catenin, and c-Myc, noted in gastric precancerous lesions. In vitro and organoid studies revealed CHI3L1's role in activating the CD44-β-catenin pathway to induce malignancy. Furthermore, our findings indicate that fibroblasts and dendritic cells are the principal sources of CHI3L1 secretion, a factor that is associated with poor prognosis in gastric cancer.</p><p><strong>Conclusions: </strong>This study highlights CHI3L1 as a key gene driving the progression from gastritis to gastric cancer, primarily by activating the CD44-β-catenin pathway, which enhances malignant cell traits. CHI3L1 is mainly secreted by fibroblasts and dendritic cells, and its high levels are linked to poor gastric cancer prognosis.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"349"},"PeriodicalIF":6.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663734","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":"TMEM176B inhibits ovarian cancer progression by regulating EMT via the Wnt/β-catenin signaling pathway.","authors":"Lili Yan, Zhaona Song, Lili Yi, Conghui Tian, Ruirui Zhang, Xuying Qin, Xiang Wang, Shaoda Ren, Xiaoping Ma, Xiaobing Wang, Xiaofeng Zhao, Feifei Wang, Jianmei Wei, Xiaodong Jia, Mingliang Gu, Fengjiao Yuan, Dianlong Jia","doi":"10.1186/s12967-025-06362-0","DOIUrl":"10.1186/s12967-025-06362-0","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is recognized as one of the deadliest forms of gynecological cancer, approximately two-thirds of patients have already developed metastasis when they are diagnosed. The function of transmembrane protein 176B (TMEM176B) in the progression of OC remains elusive. This study aimed to investigate the role and molecular mechanism of TMEM176B on OC proliferation and metastasis.</p><p><strong>Method: </strong>Expression of TMEM176B in OC and normal tissues were determined from the TCGA, GTEx, and CPTAC databases, and verified by patient-derived tissue samples. We analysed the prognostic relevance of TMEM176B in OC via Kaplan‒Meier (K‒M) survival curves and receiver operating characteristic (ROC) curves. Subsequent in vitro assays, including the CCK8 assay, colony formation assay, wound healing assay, and transwell assay, were performed to detect the influence of TMEM176B on cell proliferation and metastasis. Furthermore, a tumorigenesis study in nude mice was conducted to confirm the suppressive impact of TMEM176B on OC. RNA sequencing (RNA-seq) was utilized to uncover the mechanisms of TMEM176B on OC progression. Spearman correlation analysis was used to calculate the correlations between TMEM176B and cell adhesion, DNA replication, and the Wnt/β-catenin pathway. Finally, the role of TMEM176B in regulating the epithelial-mesenchymal transition (EMT) depending on the Wnt/β-catenin pathway was evaluated using LiCl agonist.</p><p><strong>Result: </strong>The mRNA expression of TMEM176B was significantly downregulated in OC tissues, with lower TMEM176B correlating with a worse prognosis. Moreover, higher tumor stage and tumor grade were associated with a lower TMEM176B protein level. Consistent with these findings, OC tissues exhibited significantly reduced of TMEM176B compared to normal ovarian tissue from patients. In vitro studies indicated that TMEM176B knockdown increased both the proliferation, metastasis and EMT levels of OC cells, while TMEM176B overexpression had the opposite effects. In vivo investigations reinforced that TMEM176B significantly inhibited the progression of OC. RNA-seq analysis demonstrated that TMEM176B enhanced cell adhesion, diminished DNA replication, and suppressed EMT through the regulation of the Wnt/β-catenin signaling pathway, effectively obstructing the proliferation and metastasis of OC cells and impeding the disease's progression.</p><p><strong>Conclusions: </strong>TMEM176B inhibited EMT in OC cells by controlling the activation of the Wnt/β-catenin pathway. This mechanism underscored the diagnostic and prognostic potential of TMEM176B for OC and highlights its tumor-suppressive properties as a promising therapeutic candidate.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"350"},"PeriodicalIF":6.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663692","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":"Wnt5a augments intracellular free cholesterol levels and promotes castration resistance in prostate cancer.","authors":"Yuqi Guo, Zhiyuan Zhang, Lintao Dong, Xinyi Shi, Xiaohan Li, Mingxiu Luo, Yajuan Fu, Yujing Gao","doi":"10.1186/s12967-025-06322-8","DOIUrl":"10.1186/s12967-025-06322-8","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is a leading cause of cancer-related mortality in men globally. While androgen deprivation therapy (ADT) can extend the asymptomatic phase and overall survival of patients with metastatic PCa, prolonged ADT often leads to the development of castration-resistant prostate cancer (CRPC) within 18-24 months. The mechanisms underlying CRPC remain incompletely understood, presenting a significant challenge in clinical prostate cancer treatment.</p><p><strong>Methods: </strong>In this study, we investigated the role of Wnt5a, a member of the Wnt family, in CRPC. Tumor tissues from CRPC patients were analyzed to assess the expression levels of Wnt5a. Prostate cancer cells were used to examine the impact of Wnt5a on androgen-dependent and -independent growth, as well as sensitivity to bicalutamide. RNA-seq analysis, qRT-PCR, intracellular cholesterol content and the activation of the androgen receptor (AR) signaling pathway were evaluated to elucidate the mechanistic role of Wnt5a in CRPC progression. Drug target Mendelian randomization analysis was performed to investigate the effect of PCSK9 inhibitor on prostate cancer.</p><p><strong>Results: </strong>Our study revealed a significant overexpression of Wnt5a in tissues from CRPC tumors. Wnt5a was found to enhance both androgen-dependent and -independent growth in prostate cancer cells while reducing their sensitivity to bicalutamide. Mechanistically, Wnt5a was shown to upregulate intracellular free cholesterol content and activate the AR signaling pathway, contributing to hormone therapy resistance in CRPC. PCSK9 inhibitor significantly reduced the risk of PCa.</p><p><strong>Conclusions: </strong>The findings of this study highlight a novel molecular mechanism underlying endocrine therapy resistance in CRPC mediated by Wnt5a. Targeting Wnt5a or reducing cholesterol level would be a promising therapeutic strategy for the treatment of CRPC, providing new insights into potential avenues for combating this challenging form of prostate cancer.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"347"},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657542","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":"MicroRNA-24-3p targeting Top1 in perirenal fat is involved in circulating inflammation and high cardiovascular disease risk in patients with primary aldosteronism.","authors":"Xuelin Li, Min Luo, Yanmei Zeng, Renyi Zhang, Xiaochun Lin, Yuejun Du, Wei Zhao, Qijian Feng, Minghai Wu, Jin Zhang, Lei Guo, Peili Wu, Chuyi Yang, Feifei Cai, Yuan Wang, Yuxuan Hu, Huiyun Wang, Nannan Liu, Lingling Xu, Meiping Guan","doi":"10.1186/s12967-025-06329-1","DOIUrl":"10.1186/s12967-025-06329-1","url":null,"abstract":"<p><strong>Context: </strong>Patients with primary aldosteronism (PA) are at a high risk of cardiovascular diseases (CVD) and metabolic syndrome. Notable inflammatory and fibrotic changes and differential microRNA (miRNA) expression profiles in the perirenal fat observed in PA may contribute to this increased risk, however, which has not been fully elucidated.</p><p><strong>Objective: </strong>This study aimed to explore the role of high expression of miR-24-3p in perirenal fat in circulating inflammation and its correlation with a high risk of CVD in patients with PA.</p><p><strong>Methods: </strong>Perirenal fat thickness (PRFT) measured by computed tomography (CT), miR-24-3p expression in perirenal fat, circulating inflammatory factors from adrenal veins and peripheral blood in patients with PA were analyzed. In vitro, white and brown adipocytes with miR-24-3p overexpression or inhibition respectively were stimulated with aldosterone and a unidirectional co-culture model of adipocytes and HUVEC was established. The target genes of miR-24-3p were identified.</p><p><strong>Results: </strong>Patients with PA and CVD have significantly higher PRFT than those without CVD. The expression level of miR-24-3p in perirenal fat was significantly positively correlated with PRFT. MiR-24-3p was significantly upregulated in the perirenal fat of PA and was associated with increased adipogenesis, inflammation, and oxidative stress, correlating with plasma aldosterone concentration (PAC), PRFT, cardiac remodeling, and weight gain. The IL-6 level in the peripheral blood was elevated in patients with PA and CVD, and the affected adrenal vein had the highest IL-6 level. Targeting Top1, miR-24-3p modulated aldosterone-induced effects in adipocytes and influenced IL-6 secretion, thereby affecting HUVEC.</p><p><strong>Conclusion: </strong>The upregulation of miR-24-3p in the perirenal fat induced inflammation and oxidative stress by targeting Top1, which may contribute to a high risk of CVD in patients with PA.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"345"},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657540","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":"Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer.","authors":"Xijie Zhang, Bo Ren, Bo Liu, Rui Wang, Sen Li, Yuzhou Zhao, Wence Zhou","doi":"10.1186/s12967-025-06376-8","DOIUrl":"10.1186/s12967-025-06376-8","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a comprehensive understanding of CAFs is essential for developing novel therapeutic strategies for gastric cancer.</p><p><strong>Methods: </strong>This study investigates the characteristics and functional information of CAF subtypes and explores the intercellular communication between CAFs and malignant epithelial cells (ECs) in gastric cancer by analyzing single-cell sequencing data from 24 gastric cancer samples. CellChat was employed to map intercellular communication, and Seurat was used to integrate single-cell sequencing data with spatial transcriptome data to reconstruct a comprehensive single-cell spatial map. The spatial relationship between apCAFs and cancer cells was analyzed using multicolor immunohistochemistry.</p><p><strong>Results: </strong>Cells were categorized into nine distinct categories, revealing a positive correlation between the proportions of epithelial cells (ECs) and fibroblasts. Furthermore, six fibroblast subpopulations were identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle cells (SMCs), and proliferative CAFs (pCAFs). Each of these subpopulations was linked to various biological processes and immune responses. Malignant ECs exhibited heightened intercellular communication, particularly with CAF subpopulations, through specific ligand-receptor interactions. High-density regions of CAF subpopulations displayed spatial exclusivity, with pericytes serving as a source for iCAFs, mCAFs, and apCAFs. Notably, malignant ECs and apCAFs showed increased interactions, with certain ligand-receptor pairs potentially impacting the prognosis of gastric cancer. Multiplex immunohistochemistry (mIHC) confirmed the close spatial proximity of apCAFs to cancer cells in gastric cancer.</p><p><strong>Conclusion: </strong>Our study provided a comprehensive characterization of CAF heterogeneity in gastric cancer and revealed the intricate intercellular networks within the TME. The identified CAF subpopulations and their interactions with malignant cells could serve as potential therapeutic targets.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"344"},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657541","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":"Assessing the performance of ChatGPT-4 and ChatGPT-4o in lung cancer diagnoses.","authors":"Jinru Yang, Xing Cai, Xiaofang Dai, Conghua Xie","doi":"10.1186/s12967-025-06337-1","DOIUrl":"10.1186/s12967-025-06337-1","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"346"},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657539","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":"Understanding pre-metastatic niche formation: implications for colorectal cancer liver metastasis.","authors":"Yaqin Li, Hong Wang, Dengxuan Mao, Xiaoyu Che, Yan Chen, Yuping Liu","doi":"10.1186/s12967-025-06328-2","DOIUrl":"10.1186/s12967-025-06328-2","url":null,"abstract":"<p><p>The liver is the most commonly metastasized organ in colorectal cancer (CRC), and distant metastasis is the primary cause of mortality from CRC. In recent years, researchers have discovered that tumor cells create a \"pre-metastatic niche (PMN)\" favorable to metastasis before reaching the metastatic location. This review discusses the many processes and mechanisms that lead to PMN formation in CRC, including gut microbiota, stem cell stimulation, immunocyte interactions, and the induction of extracellular vesicles that carry important information. It examines research methods and diagnostic and therapeutic approaches for treating metastatic CRC with PMN. The crucial significance of PMN formation in metastatic CRC is also highlighted.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"340"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649547","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":"SET7 lysine methyltransferase mediates the up-regulation of NADPH oxidase expression, oxidative stress, and NLRP3 inflammasome priming in atherosclerosis.","authors":"Simona-Adriana Manea, Mihaela-Loredana Vlad, Alexandra-Gela Lazar, Horia Muresian, Maya Simionescu, Adrian Manea","doi":"10.1186/s12967-025-06338-0","DOIUrl":"10.1186/s12967-025-06338-0","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of histone methylation-based epigenetic mechanisms leads to either transient or long-lasting transcriptomic alterations in vascular and immune cells with important consequences on atherosclerotic plaque development and stability. We hypothesized that the epigenetic enzyme SET7 lysine methyltransferase contributes to the up-regulation of NADPH oxidase (Nox) and NLRP3 inflammasome expression in atherosclerosis.</p><p><strong>Methods: </strong>To test this hypothesis, we examined human non-atherosclerotic and atherosclerotic tissue samples, apolipoprotein E-deficient (ApoE-/-) mice, and human macrophages (Mac) employing real-time PCR, Western blot, immunofluorescence microscopy, and histological techniques. Male ApoE-/- mice with established atherosclerosis were randomized to receive concomitant with the high-fat diet, 5 mg/kg (R)-PFI-2, a selective SET7 pharmacological inhibitor, or its vehicle, every other day for 4 weeks.</p><p><strong>Results: </strong>The results revealed that SET7 mRNA and protein, and H3K4me1 levels were significantly elevated in human carotid atherosclerotic lesions, aorta of atherosclerotic mice, and in cultured pro-inflammatory Mac. In the atherosclerotic mice, pharmacological blockade of SET7 catalytic activity with the specific inhibitor, significantly reduced atherosclerotic plaque development, decreased the aortic up-regulation of mRNA and protein levels of Nox catalytic subunits, mitigated the formation of NT-/4HNE-protein adducts, attenuated NLRP3 gene and protein expression, and reduced pro-caspase-1 and pro-IL18 cleavage. In polarized pro-inflammatory human M1-Mac, SET7-oriented pharmacological intervention reduced the transcriptional up-regulation of Nox catalytic subunits, NLRP3, caspase-1, IL1β, and IL18, and the secretion IL1β and TNFα. Transient overexpression of SET7 in human endothelial cells enhanced mRNA levels of Nox1, Nox2, Nox4, Nox5, and p22phox.</p><p><strong>Conclusion: </strong>The novel results show that SET7 regulates important mechanisms leading to enhanced formation of reactive oxygen species and pro-inflammatory cytokines release in atherosclerosis. The data recommend SET7 as a promising target for pharmacological interventions and as supportive therapeutic strategy in atherosclerotic cardiovascular diseases.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"339"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649543","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":"Metabolic state uncovers prognosis insights of esophageal squamous cell carcinoma patients.","authors":"Tingze Feng, Pengfei Li, Siyi Li, Yuhan Wang, Jing Lv, Tian Xia, Hoy-Jong Lee, Hai-Long Piao, Di Chen, Yegang Ma","doi":"10.1186/s12967-025-06087-0","DOIUrl":"10.1186/s12967-025-06087-0","url":null,"abstract":"<p><strong>Background: </strong>Metabolite-protein interactions (MPIs) are crucial regulators of cancer metabolism; however, their roles and coordination within the esophageal squamous cell carcinoma (ESCC) microenvironment remain largely unexplored. This study is the first to comprehensively map the metabolic landscape of the ESCC microenvironment by integrating an MPI network with multi-scale transcriptomics data.</p><p><strong>Methods: </strong>First, we characterized the metabolic states of cells in ESCC using single-cell transcriptome profiles of key metabolite-interacting proteins. Next, we determined the metabolic patterns of each ESCC patient based on the composition of different metabolic states within bulk samples. Finally, the ESCC samples were clustered into unique subtypes.</p><p><strong>Results: </strong>Sixteen ESCC metabolic states across 7 cell types were identified based on the re-analysis of single-cell RNA-sequencing data of 208,659 cells in 64 ESCC samples. Each of the 7 cell types within the tumor microenvironment exhibited distinct metabolic states, highlighting the high metabolic heterogeneity of ESCC. Based on differences in the compositions of the metabolic states, 4 ESCC subtypes were identified in two independent cohorts (n = 79 and 119), which were associated with significant variations in prognosis, clinical features, gene expression, and pathways. Notably, the inactivation of cellular detoxification processes may contribute to the poor prognosis of ESCC patients.</p><p><strong>Conclusions: </strong>Overall, we redefined robust ESCC prognostic subtypes and identified key MPI pathways that link metabolism to tumor heterogeneity. This study provides the first comprehensive mapping of the ESCC metabolic microenvironment, offering novel insights into ESCC metabolic diversity and its clinical applications.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"342"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649487","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":"New insights on anti-tumor immunity of CD8⁺ T cells: cancer stem cells, tumor immune microenvironment and immunotherapy.","authors":"Yibin Lin, Yifu Song, Yaochuan Zhang, Xiaodong Li, Liang Kan, Sheng Han","doi":"10.1186/s12967-025-06291-y","DOIUrl":"10.1186/s12967-025-06291-y","url":null,"abstract":"<p><p>Recent breakthroughs in tumor immunotherapy have confirmed the capacity of the immune system to fight several cancers. The effective means of treating cancer involves accelerating the death of tumor cells and improving patient immunity. Dynamic changes in the tumor immune microenvironment alter the actual effects of anti-tumor drug production and may trigger favorable or unfavorable immune responses by modulating tumor-infiltrating lymphocytes. Notably, CD8⁺ T cells are one of the primary tumor-infiltrating immune cells that provide anti-tumor response. Tumor cells and tumor stem cells will resist or evade destruction through various mechanisms as CD8⁺ T cells exert their anti-tumor function. This paper reviews the research on the regulation of tumor development and prognosis by cancer stem cells that directly or indirectly alter the role of tumor-infiltrating CD8⁺ T cells. We also discuss related immunotherapy strategies.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"341"},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649490","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}