Journal of Translational Medicine最新文献

{"title":"Exposure of monocyte-derived macrophages to the UV-inactivated SARS-CoV-2 VOCs shows similar effects on the transcriptomic profile as active virus: a comparative analysis.","authors":"Josè Camilla Sammartino, Roberta Vazzana, Nicola Cuscino, Salvatore Castelbuono, Roberto Giambruno, Claudia Carcione, Vitale Miceli, Matteo Bulati, Daniele Lilleri, Pier Giulio Conaldi, Fausto Baldanti, Alessia Gallo, Irene Cassaniti","doi":"10.1186/s12967-025-06264-1","DOIUrl":"10.1186/s12967-025-06264-1","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"332"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634266","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":"Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation.","authors":"Feng Xiang, Zhimin Zhang, Jingchen Xie, Suhui Xiong, Chen Yang, Duanfang Liao, Bohou Xia, Limei Lin","doi":"10.1186/s12967-025-06341-5","DOIUrl":"10.1186/s12967-025-06341-5","url":null,"abstract":"<p><p>Traditionally, the carnitine pool is closely related to fatty acid metabolism. However, with increasing research, the pleiotropic effects of the carnitine pool have gradually emerged. The purpose of this review is to comprehensively investigate of the emerging understanding of the pleiotropic role of the carnitine pool, carnitine/acylcarnitines are not only auxiliaries or metabolites of fatty acid oxidation, but also play more complex and diverse roles, including energy metabolism, mitochondrial homeostasis, epigenetic regulation, regulation of inflammation and the immune system, tumor biology, signal transduction, and neuroprotection. This review provides an overview of the complex network of carnitine synthesis, transport, shuttle, and regulation, carnitine/acylcarnitines have the potential to be used as communication molecules, biomarkers and therapeutic targets for multiple diseases, with profound effects on intercellular communication, metabolic interactions between organs and overall metabolic health. The purpose of this review is to comprehensively summarize the multidimensional biological effects of the carnitine pool beyond its traditional role in fatty acid oxidation and to summarize the systemic effects mediated by carnitine/acylcarnitine to provide new perspectives for pharmacological research and treatment innovation and new strategies for the prevention and treatment of a variety of diseases.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"324"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634259","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":"Gut Microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients.","authors":"Paula L Scalzo, Austin G Marshall, Sirena Soriano, Kristen Curry, Mario Dulay, Timea Hodics, Eamonn M M Quigley, Todd J Treangen, María M Piskorz, Sonia Villapol","doi":"10.1186/s12967-025-06348-y","DOIUrl":"10.1186/s12967-025-06348-y","url":null,"abstract":"<p><strong>Background: </strong>Infection with SARS-CoV-2, the virus responsible for COVID-19, can lead to a range of physical symptoms and mental health challenges, including stress, anxiety, and depression. These effects are particularly pronounced in hospitalized patients, likely due to the virus's direct and indirect impact on the nervous system. Gut dysbiosis, an imbalance in the gut microbiome, has been implicated in immune dysfunction and chronic inflammation in COVID-19 patients. However, the interactions between gut microbiome composition and the physical and mental symptoms of COVID-19 remain incompletely understood.</p><p><strong>Methods: </strong>We investigated the association between physical and mental symptoms, cytokine profiles, and gut microbiota composition in 124 hospitalized COVID-19 patients. We collected data on demographics, COVID-19 severity, and mental health indicators (stress, anxiety, and depression). Gut microbiome profiling was performed using full-length 16 S rRNA gene sequencing to evaluate microbial diversity and composition.</p><p><strong>Results: </strong>COVID-19 severity was categorized as low (27.4%), moderate (29.8%), or critical (42.8%). Common symptoms included fever (66.1%) and cough (55.6%), while somatic symptoms (27.3%), anxiety (27.3%), depressive symptoms (39%), and stress (80.5%) were frequently self-reported. Elevated interleukin-6 levels in severe cases highlighted systemic inflammation, reduced gut bacterial diversity, particularly among women and obese patients, correlated with higher disease severity. Notably, the genus Mitsuokella was associated with increased physical symptoms and mental distress, while Granulicatella was linked to critical illness.</p><p><strong>Conclusions: </strong>Our findings reveal significant associations between mental health status, systemic inflammation, and gut dysbiosis in hospitalized COVID-19 patients. These results indicate the potential for microbiome-targeted therapies to mitigate psychological and physical complications and improve recovery outcomes in this population.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"327"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634305","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 NcRNA/Wnt axis in lung cancer: oncogenic mechanisms, remarkable indicators and therapeutic targets.","authors":"Yang Zhong, Jia-Wei He, Chun-Xia Huang, Heng-Zhou Lai, Xue-Ke Li, Chuan Zheng, Xi Fu, Feng-Ming You, Qiong Ma","doi":"10.1186/s12967-025-06326-4","DOIUrl":"10.1186/s12967-025-06326-4","url":null,"abstract":"<p><p>Early diagnosis of lung cancer (LC) is challenging, treatment options are limited, and treatment resistance leads to poor prognosis and management in most patients. The Wnt/β-catenin signaling pathway plays a vital role in the occurrence, progression, and therapeutic response of LC. Recent studies indicate that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as epigenetic regulators that can promote or inhibit Wnt/β-catenin signaling by interacting with Wnt proteins, receptors, signaling transducers, and transcriptional effectors, thereby affecting LC cell proliferation, metastasis, invasion, and treatment resistance. Deepening our understanding of the regulatory network between ncRNAs and the Wnt/β-catenin signaling pathway will help overcome the limitations of current LC diagnosis and treatment methods. This article comprehensively reviews the regulatory mechanisms related to the functions of ncRNAs and the Wnt/β-catenin pathway in LC, examining their potential as diagnostic and prognostic biomarkers and therapeutic targets, aiming to offer new promising perspectives for LC diagnosis and treatment.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"326"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634084","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":"Letter: Time to correct the record on the global burden of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).","authors":"Maya Vardaman, Stuart Gilmour","doi":"10.1186/s12967-025-06281-0","DOIUrl":"10.1186/s12967-025-06281-0","url":null,"abstract":"","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"331"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633789","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 differences in intestinal flora and metabolites between H-type hypertension and non-H-type hypertension.","authors":"Jian Wu, Jiangman Zhao, Yinhong Cheng, Haoliang Zhou, Guanqiao Shen, Hongying Ding, Jin Lv, Shiye Dong, Oushan Tang","doi":"10.1186/s12967-025-06295-8","DOIUrl":"10.1186/s12967-025-06295-8","url":null,"abstract":"<p><strong>Objective: </strong>In order to explore the differences in gut microbiota and their metabolites between patients with H-type hypertension and non-H-type hypertension.</p><p><strong>Method: </strong>Our study included 100 hypertensive patients from the Department of Cardiology at Shaoxing Second Hospital, with 51 patients having H-type hypertension (H group) and 49 having non-H-type hypertension (non-H group). Blood samples were collected for clinical and metabolite testing, and fecal samples were collected for 16 S rRNA sequencing and metabolite testing.</p><p><strong>Results: </strong>No significant difference in the α and β diversity of the gut microbiota between the two groups of patients were observed. However, at the phylum level, patients in the non-H group have a higher abundance of Firmicutes and a lower abundance of Actinobacteriota. At the genus level, compared to the non-H group, the H-type group has a higher abundance of Bifidobacterium; at the species level, the Non-H group has a higher abundance of Bacteroides vulgatus and lower abundances of Bacteroides stercoris and Bacteroides plebeius. In the serum of both groups, the concentrations of Acetate and Isobutyrate were significantly higher in the H group (P < 0.05), while in the feces of both groups of patients, the concentration of Malonate was significantly higher in the Non-H group.</p><p><strong>Conclusion: </strong>The microbial sequencing shows distinct differences between the H and non-H groups, with the latter having higher Firmicutes and Bacteroides vulgatus, while the H group has more Bifidobacterium and higher serum acetate levels. These variations suggest unique gut microbiota compositions and metabolite profiles for each group.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"329"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634081","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":"Short-term oral zinc supplementation enhances Natural Killer cell functionality and decreases circulating Innate Lymphoid Cell counts and frequencies in healthy young adults.","authors":"Lara Amling, Lothar Rink, Sabrina B Bennstein","doi":"10.1186/s12967-025-06259-y","DOIUrl":"10.1186/s12967-025-06259-y","url":null,"abstract":"<p><strong>Background: </strong>Zinc is an essential trace element with high importance for immune function. Previous research has shown that vegetarians and vegans are at increased risk of zinc deficiency, due to low zinc bioavailability in plant-based food. However, its effects on immune parameters in healthy adults following these diets remain largely unexplored. Therefore, this study investigated the effects of dietary patterns, serum zinc levels, and short-term oral zinc supplementation on Natural Killer (NK) cells, circulating Innate Lymphoid Cells (cILCs), and NK cell functionality in omnivores, vegetarians, and vegans.</p><p><strong>Methods: </strong>A total of 54 study participants, including 21 omnivores, 18 vegetarians, and 15 vegans were enrolled in our study. NK cell and cILC counts and frequencies were analyzed by flow cytometry and NK cell cytotoxicity assay was performed and compared between the three dietary cohorts as well as between zinc adequate (ZA) and zinc deficient (ZD) individuals. Based on serum zinc concentrations and/or Food Frequency Questionnaire (FFQ) scores, study participants classified as ZD were supplemented with 10 mg zinc daily for 14 days. After this period, the same experiments were performed.</p><p><strong>Results: </strong>Our results show that neither dietary patterns nor baseline zinc levels significantly affect cILC or NK cell counts, frequencies, or NK cell cytotoxicity. However, short-term oral zinc supplementation significantly reduced cILC counts and frequencies, while enhancing NK cell functionality. Here, NK cell cytotoxicity is significantly positively correlated, whereas cILC counts are negatively correlated with serum zinc concentrations. Remarkably, 72% of all study participants, including 48% of omnivores, were classified as ZD.</p><p><strong>Conclusions: </strong>Since proper NK cell functionality is required for early defense against infected or malignant cells, and cILCs act as progenitors to replenish tissue resident ILCs, which are crucial for tissue homeostasis and barrier integrity, our results suggest that routine zinc supplementation might be a simple yet effective strategy to enhance immune defense and potentially prevent diseases across different dietary groups.</p><p><strong>Trial registration: </strong>The study was approved and registered by the Institutional Ethics Committee of the Medical Faculty of RWTH Aachen University on the 19th of July 2023 (study numbers: EK 23-148 and EK 23-234, CTC number: 23-163).</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"333"},"PeriodicalIF":6.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634077","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":"Machine learning-derived diagnostic model of epithelial ovarian cancer based on gut microbiome signatures.","authors":"Cheng Chen, Chengyuan Deng, Yanwen Li, Shuguang He, Yunhong Liu, Shuwen Pan, Wenqian Xu, Lu Fang, Yixi Zhu, Yingying Wang, Xiaoxin Jiang","doi":"10.1186/s12967-025-06339-z","DOIUrl":"10.1186/s12967-025-06339-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Prior studies have elucidated that alterations in gut microbiota are associated with a spectrum of tumors and metabolic disorders. However, the diagnostic value of gut microbiota in epithelial ovarian cancer remains insufficiently investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 34 patients with a diagnosis of epithelial ovarian cancer (EOC), 15 patients with benign ovarian tumors (TB), and 30 healthy volunteers (NOR) were enrolled in this study. Fecal samples were collected, followed by sequencing of the V3-V4 region of the 16S rRNA gene. The clinical data and pathological characteristics were comprehensively recorded for further analysis, PICRUSt2 was utilized to conduct an analysis of microbial functional predictions, WGCNA networks were constructed by integrating microbiome and clinical data. LEfSe analysis was employed to identify microbial diagnostic markers, LASSO and SVM analyses were used to screen microbial diagnostic markers in conjunction with the Cally index, to establish a Microbial-Cally diagnostic model. Bootstrap resampling was utilized for the internal validation of the model, whereas the Hosmer-Lemeshow test and decision curve analysis (DCA) were employed to evaluate the diagnostic performance of the model. Plasma samples were subjected to untargeted metabolomics profiling, followed by differential analysis to identify key metabolites that are significantly altered in epithelial ovarian cancer. At the same time, Spearman correlation analysis was used to study the association between key microbiota and differential metabolites. The supernatants from Escherichia coli and Bifidobacterium cultures were co-cultured with SKOV3 cells. Cell proliferation, migration, and invasion were evaluated using Cell Counting Kit-8 (CCK-8) assay, Transwell migration and invasion assays. Apoptosis was assessed by flow cytometry analysis of fluorescence signals from Annexin V and propidium iodide (PI) staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared to Nor and TB populations, individuals diagnosed with EOC demonstrated a significantly diminished gut microbiota diversity when contrasted with both normal controls and those presenting benign conditions. Specifically, the relative abundance of Bilophila, Bifidobacterium, and other probiotics was significantly reduced in patients diagnosed with epithelial ovarian cancer (EOC), while Escherichia and Shigella demonstrated a marked enrichment within this cohort. Differential microorganisms were identified through the application of machine learning techniques to delineate the characteristic microbial profiles associated with the EOC patients. A significant correlation was identified between the Cally index and microorganisms. In conclusion, we utilized microbial biomarkers alongside the Cally to establish a diagnostic model for epithelial ovarian cancer, receiver operating characteristic (ROC) curve Area Under Curve (AUC) of 0.976 (95%CI 0.943-1.00), The AUC obtained","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"319"},"PeriodicalIF":6.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625062","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":"N6-methyladenosine RNA modified BAIAP2L2 facilitates extracellular vesicles-mediated chemoresistance transmission in gastric cancer.","authors":"Yuhan Liao, Xinhua Chen, Hao Xu, Yunfei Zhi, Xinghua Zhuo, Jiang Yu, Liang Zhao","doi":"10.1186/s12967-025-06340-6","DOIUrl":"10.1186/s12967-025-06340-6","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) produced in the tumor microenvironment in response to chemotherapy promote chemotherapy-resistant phenotypes. However, the role of EVs proteins induced by gastric cancer (GC) cell chemotherapy in regulating chemotherapy resistance remains unclear.</p><p><strong>Methods: </strong>Immunohistochemistry was used to verify the relationship between brain-specific angiogenesis inhibitor 1-associated protein-2-like protein 2 (BAIAP2L2) expression and chemotherapy resistance in advanced GC. The relationship between BAIAP2L2 and chemotherapy resistance was verified using a subcutaneous tumor model in nude mice. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were performed to detect purified EVs. Tandem mass tag (TMT) analysis was used to detect differential labels. The interaction between YTH domain-containing family protein1 (YTHDF1) and BAIAP2L2 in GC cells was confirmed by RIP-qPCR analysis using a YTHDF1-specific antibody.</p><p><strong>Results: </strong>We found that BAIAP2L2 was associated with chemotherapy resistance to GC in clinical samples and was increased in chemotherapy-resistant GC cells. Mechanistically, BAIAP2L2 promotes the transfer of chemotherapy resistance from resistant GC cells to sensitive cells through EVs proteins, such as ANXA4. Furthermore, ANXA4 promoted platinum-based chemical resistance in GC by mediating autophagy. Interestingly, YTHDF1 facilitates the translation of BAIAP2L2 and ANXA4 through m⁶A modifications.</p><p><strong>Conclusions: </strong>Our findings reveal the key role of BAIAP2L2 as a potential prognostic marker and therapeutic target for chemotherapy resistance in GC.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"320"},"PeriodicalIF":6.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625069","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":"PD-L1⁺ CD49f⁺ CD133⁺ Circulating tumor cells predict outcome of patients with vulvar or cervical cancer after radio- and chemoradiotherapy.","authors":"Selina Gies, Patrick Melchior, Istvan Molnar, Gregor Olmes, Russalina Stroeder, Tanja Tänzer, Maike Pohlers, Moritz Schäfer, Laura Theobald, Martina Sester, Erich Franz Solomayer, Barbara Walch-Rückheim","doi":"10.1186/s12967-025-06277-w","DOIUrl":"10.1186/s12967-025-06277-w","url":null,"abstract":"<p><strong>Background: </strong>Monitoring individual therapy responses of patients with cancer represents a major clinical challenge providing the basis to early identify metastases and cancer relapse. We previously demonstrated that radio- or chemoradiotherapy affects the systemic cellular milieu of patients with vulvar or cervical cancer and creates individual post-therapeutic environments associated with cancer relapse. Circulating tumor cells (CTCs) in the systemic milieu are related to metastases and relapse; however, their quantitative and phenotypic characteristics during therapy of patients with vulvar and cervical cancer are still unknown.</p><p><strong>Methods: </strong>In this prospective, longitudinal study, we verified the presence of CTCs via immunofluorescence and systemically characterized CTCs by flow cytometry from the blood of 40 patients with vulvar and 115 patients with cervical cancer receiving surgery, adjuvant radiotherapy (aRT), chemoradiotherapy (aCRT) or primary chemoradiotherapy (pCRT) and linked the presence of different CTC subpopulations with individual outcome of disease.</p><p><strong>Results: </strong>Pre-therapeutic cytokeratin⁺ CD45^- CTC numbers significantly correlated with tumor FIGO stages, lymph node metastases and relapse. While surgery only did not significantly alter CTC occurrence, aRT and aCRT as well as pCRT differentially decreased or increased CTCs in patients with both tumor entities compared to baseline levels. Therapy-mediated increased CTC numbers were directly linked with subsequent cancer recurrence on follow-up. Phenotypic characterization of CTCs revealed enhanced expression of the stem cell marker CD133 as well as the integrin α6 (CD49f) after aRT, aCRT and pCRT. Furthermore, the aRT, aCRT and pCRT cohorts exhibited increased proportions of Programmed Cell Death Protein Ligand (PD-L1) expressing cells among post-therapeutic CTCs. Notably, post-therapeutic PD-L1⁺ CD49f⁺ CD133⁺ numbers ≥ 5/ml in patients with vulvar cancer and ≥ 2/ml in patients with cervical cancer were associated with reduced recurrence-free survival on follow-up.</p><p><strong>Conclusion: </strong>Our study unravels individual therapy-induced changes in CTC phenotypic characteristics and occurrence in the patients' blood and their association with cancer relapse. Our results may help to explain differences in the individual courses of disease of patients with vulvar and cervical cancer and suggest PD-L1, CD49f and CD133 as targets for immunotherapy in vulvar and cervical cancer.</p>","PeriodicalId":17458,"journal":{"name":"Journal of Translational Medicine","volume":"23 1","pages":"321"},"PeriodicalIF":6.1,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625073","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}