Biomarker Research最新文献

{"title":"Progress in multi-omics studies of osteoarthritis.","authors":"Yuanyuan Wei, He Qian, Xiaoyu Zhang, Jian Wang, Heguo Yan, Niqin Xiao, Sanjin Zeng, Bingbing Chen, Qianqian Yang, Hongting Lu, Jing Xie, Zhaohu Xie, Dongdong Qin, Zhaofu Li","doi":"10.1186/s40364-025-00732-y","DOIUrl":"10.1186/s40364-025-00732-y","url":null,"abstract":"<p><p>Osteoarthritis (OA), a ubiquitous degenerative joint disorder, is marked by pain and disability, profoundly impacting patients' quality of life. As the population ages, the global prevalence of OA is escalating. Omics technologies have become instrumental in investigating complex diseases like OA, offering comprehensive insights into its pathogenesis and progression by uncovering disease-specific alterations across genomics, transcriptomics, proteomics, and metabolomics levels. In this review, we systematically analyzed and summarized the application and recent achievements of omics technologies in OA research by scouring relevant literature in databases such as PubMed. These studies have shed light on new potential therapeutic targets and biomarkers, charting fresh avenues for OA diagnosis and treatment. Furthermore, in our discussion, we highlighted the immense potential of spatial omics technologies in unraveling the molecular mechanisms of OA and in the development of novel therapeutic strategies, proposing future research directions and challenges. Collectively, this study encapsulates the pivotal advances in current OA research and prospects for future investigation, providing invaluable references for a deeper understanding and treatment of OA. This review aims to synthesize the recent progress of omics technologies in the realm of OA, aspiring to furnish theoretical foundations and research orientations for more profound studies of OA in the future.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"26"},"PeriodicalIF":9.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400735","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":"BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia.","authors":"Annalisa Chiarenza, Gaia Vertillo Aluisio, Nunziatina Laura Parrinello, Sara Marino, Anna Maria Corsale, Grete Francesca Privitera, MojtabaShekarkar Azgomi, Enrico La Spina, Daniela Cambria, Angelo Curtopelle, Gaetano Isola, Cirino Botta, Francesco Di Raimondo, Alessandra Romano, Maria Santagati","doi":"10.1186/s40364-025-00734-w","DOIUrl":"10.1186/s40364-025-00734-w","url":null,"abstract":"<p><strong>Background: </strong>In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment.</p><p><strong>Methods: </strong>To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine.</p><p><strong>Results: </strong>In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2. In FL patients, vaccination induced expansion of central memory CD8 + CD57dim CD279 + T cells and reduction of the neutrophil subset myeloid 1 (CD14^-CD15⁺CD16^dimCD64⁺CD33^-CD38⁺PDL1⁺HLA-DR^-); in both cohorts, CD45RA + CD27 + CD279 + NK cells were expanded after a full cycle of vaccination. After vaccination, the genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus and Lactobacillus increased in both CLL patients and FL patients, whereas Faecalibacterium, Enterobacteriacae, and Enterococcus decreased. Multivariate analysis failed to identify factors associated with changes in microbiome communities among the CLL and FL cohorts, considering age, sex, exposure to anti-CD20 therapy and disease activity. Only in FL patients, alpha diversity was negatively correlated with neutrophil subsets myeloid 1 e 5 at baseline and positively correlated with neutrophil subset 6 after vaccination. PICRUSt2 analysis showed how microbiome can also affect the host health promoting chronic inflammation. The L-lysine biosynthesis pathway was more represented in CLL patients, whereas the L-valine degradation pathway and the anaerobic degradation of purine nucleobases were overrepresented in the FL cohort.</p><p><strong>Conclusions: </strong>Taken together, our findings reveal the effect of the BNT162b2 vaccine in shaping the microbiome composition in CLL and FL patients, despite receiving treatment for their underlying active disease, and highlight the importance of a comprehensive analysis of the immunome and microbiome profiling to understand immune function in these cohorts of patients.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"25"},"PeriodicalIF":9.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392256","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":"Prognostic utility of neutrophil gelatinase-associated lipocalin (NGAL) levels for cardiovascular events in patients with stable coronary artery disease treated with percutaneous coronary intervention: a prospective longitudinal cohort study.","authors":"Ting-Yu Lin, Hsin-Bang Leu, Yen-Wen Wu, Wei-Kung Tseng, Tsung-Hsien Lin, Hung-I Yeh, Kuan-Cheng Chang, Ji-Hung Wang, Wei-Hsian Yin, Chau-Chung Wu, Chun-Yao Huang, Shing-Jong Lin, Chien-Yi Hsu, Jaw-Wen Chen","doi":"10.1186/s40364-025-00737-7","DOIUrl":"10.1186/s40364-025-00737-7","url":null,"abstract":"<p><strong>Introduction: </strong>Neutrophil gelatinase-associated lipocalin (NGAL) modulates the enzymatic activity of matrix metalloproteinase-9, which is an important mediator of plaque instability in atherosclerosis. High NGAL levels can independently predict all-cause mortality and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). However, studies that have measured NGAL levels in patients with stable coronary artery disease (CAD) are limited. Furthermore, no significant prognostic predictive value between NGAL levels and stable CAD has been established.</p><p><strong>Hypothesis: </strong>We aimed to investigate the prognostic role of NGAL levels in a prospective cohort study of patients with stable CAD treated with percutaneous coronary intervention (PCI).</p><p><strong>Methods: </strong>A total of 2,238 stable patients with CAD and a previous PCI were enrolled in a multicenter prospective observational study (The National Taiwan Biosignature Research, NTBR) in Taiwan. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal myocardial infarction, and ischemic stroke). The secondary outcome was a composite of cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure).</p><p><strong>Results: </strong>During the mean follow-up period of 4.6 ± 1.7 years, 441 patients reached the primary endpoints. Kaplan-Meier analysis showed that event-free survival was significantly different between the first and third tertile groups (log-rank test, p < 0.001) in subjects categorized by NGAL levels. In a multivariate Cox proportional hazard regression analysis, plasma NGAL levels were independently associated with an increased risk of MACE [adjusted hazard ratio (aHR) = 1.35; 95% confidence interval (CI) = 1.18-1.54, p < 0.001], AMI (aHR = 1.34; 95% CI = 1.12-1.59, p < 0.001), and target vessel revascularization (aHR = 1.35; 95% CI = 1.19-1.53, p < 0.001). Addition of serum NGAL levels to the traditional risk model improved its prediction value for future cardiovascular events.</p><p><strong>Conclusions: </strong>High plasma NGAL levels were independently associated with the occurrence of MACE and composite cardiovascular events in patients with stable PCI-treat CAD.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"24"},"PeriodicalIF":9.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371428","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":"Advances in engineered T cell immunotherapy for autoimmune and other non-oncological diseases.","authors":"Qiaolin Huang, Xiaojian Zhu, Yicheng Zhang","doi":"10.1186/s40364-025-00736-8","DOIUrl":"10.1186/s40364-025-00736-8","url":null,"abstract":"<p><p>Adoptive immunotherapy using engineered T cells expressing chimeric antigen receptors has shown remarkable success in treating patients with hematological malignancies. However, realizing broader therapeutic applications of engineered T cells in other diseases requires further exploration in clinical investigations. In this review, we highlight recent advances in the engineering of T cells in non-oncology areas, including autoimmune and inflammatory diseases, infections, fibrosis, hemophilia, and aging. Chimeric antigen receptor immunotherapy has shown good outcomes in non-oncology areas, but many challenges remain in improving its safety and efficacy and and expanding its application to the treatment of non-oncological diseases.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"23"},"PeriodicalIF":9.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123997","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 BATF in immune cell differentiation and autoimmune diseases.","authors":"Xiaomeng Wang, Yue Hong, Jinmei Zou, Bo Zhu, Chao Jiang, Liwei Lu, Jie Tian, Jing Yang, Ke Rui","doi":"10.1186/s40364-025-00733-x","DOIUrl":"10.1186/s40364-025-00733-x","url":null,"abstract":"<p><p>As a member of the Activator Protein-1 (AP-1) transcription factor family, the Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions of immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles in innate and adaptive immune responses but also acts as a crucial factor in the differentiation and function of various immune cells. Lines of evidence indicate that BATF is associated with the onset and progression of allergic diseases, graft-versus-host disease, tumors, and autoimmune diseases. This review summarizes the roles of BATF in the development and function of innate and adaptive immune cells, as well as its immunoregulatory effects in the development of autoimmune diseases, which may enhance the current understanding of the pathogenesis of autoimmune diseases and facilitate the development of new therapeutic strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"22"},"PeriodicalIF":9.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061408","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":"Chemotherapy in synergy with innate immune agonists enhances T cell priming for checkpoint inhibitor treatment in pancreatic cancer.","authors":"Nan Niu, Keyu Li, Junke Wang, Vanessa Funes, Birginia Espinoza, Pan Li, Jianxin Wang, Melissa Lyman, Mengni He, Brian Herbst, Michael Wichroski, Ruslan Novosiadly, Sami Shoucair, Yiping Mou, Lei Zheng","doi":"10.1186/s40364-024-00721-7","DOIUrl":"10.1186/s40364-024-00721-7","url":null,"abstract":"<p><strong>Background: </strong>The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.</p><p><strong>Methods: </strong>We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.</p><p><strong>Results: </strong>We found that innate agonists potentiate the role of chemotherapy in inducing effector T cells and subsequently to prime the tumor microenvironment (TME) better for ICI treatments. Triple combination of chemotherapy, innate agonists, and ICIs is superior to single modalities or double modalities in antitumor efficacies. Adding chemotherapy to innate agonists enhances the infiltration of overall CD8⁺ T cells and the memory cytotoxic subtype. NLRP3 agonist has a less effect than STING agonist on driving the T cell exhaustion. Adding chemotherapy to innate agonists enhances the infiltration of dendritic cells (DCs) in the tumors and CD86⁺ mature DCs in tumor draining lymph nodes. RNA sequencing analysis of the pancreatic tumors demonstrates the role of the combination of STING/NLRP3 agonist and chemotherapy, but not either treatment modality alone, in upregulating the T cell activation signaling. The NLRP3 agonist-mediated T cell activation is likely through regulating the nitrogen metabolism pathways.</p><p><strong>Conclusion: </strong>This study supports the clinical testing of both STING and NLRP3 agonists, respectively, in combination with chemotherapy to sensitize PDAC patients for ICI treatments.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"21"},"PeriodicalIF":9.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054280","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":"Noninvasive in vivo imaging of macrophages: understanding tumor microenvironments and delivery of therapeutics.","authors":"Prakash Gangadaran, Akanksha Onkar, Ramya Lakshmi Rajendran, Anshika Goenka, Ji Min Oh, Fatima Khan, ArulJothi Kandasamy Nagarajan, Sathish Muthu, Anand Krishnan, Chae Moon Hong, Byeong-Cheol Ahn","doi":"10.1186/s40364-025-00735-9","DOIUrl":"10.1186/s40364-025-00735-9","url":null,"abstract":"<p><p>Macrophages are pivotal in the body's defense and response to inflammation. They are present in significant numbers and are widely implicated in various diseases, including cancer. While molecular and histological techniques have advanced our understanding of macrophage biology, their precise function within the cancerous microenvironments remains underexplored. Enhancing our knowledge of macrophages and the dynamics of their extracellular vesicles (EVs) in cancer development can potentially improve therapeutic management. Notably, macrophages have also been harnessed to deliver drugs. Noninvasive in vivo molecular imaging of macrophages is crucial for investigating intricate cellular processes, comprehending the underlying mechanisms of diseases, tracking cells and EVs' migration, and devising macrophage-dependent drug-delivery systems in living organisms. Thus, in vivo imaging of macrophages has become an indispensable tool in biomedical research. The integration of multimodal imaging approaches and the continued development of novel contrast agents hold promise for overcoming current limitations and expanding the applications of macrophage imaging. This study comprehensively reviews several methods for labeling macrophages and various imaging modalities, assessing the merits and drawbacks of each approach. The review concludes by offering insights into the applicability of molecular imaging techniques for real time monitoring of macrophages in preclinical and clinical scenarios.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"20"},"PeriodicalIF":9.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048473","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":"Dysregulation of transposable elements and PIWI-interacting RNAs in myelodysplastic neoplasms.","authors":"Zdenek Krejcik, David Kundrat, Jiri Klema, Andrea Hrustincova, Iva Trsova, Monika Belickova, Jaroslav Cermak, Anna Jonasova, Jiri Dostal, Michaela Dostalova Merkerova","doi":"10.1186/s40364-025-00725-x","DOIUrl":"10.1186/s40364-025-00725-x","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear.</p><p><strong>Methods: </strong>In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients.</p><p><strong>Results: </strong>Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity.</p><p><strong>Conclusions: </strong>Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"13"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030296","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":"Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis.","authors":"Heng Li, Cheng Xing, Ji Li, Yihao Zhan, Ming Luo, Peilong Wang, Yue Sheng, Hongling Peng","doi":"10.1186/s40364-024-00723-5","DOIUrl":"10.1186/s40364-024-00723-5","url":null,"abstract":"<p><p>Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA-seq) and high-throughput chromosome conformation capture (Hi-C) sequencing. Over 10,000 cells were profiled via scRNA-seq, revealing the comprehensive B cell transformation in RS. Hi-C sequencing exposed a unique chromatin architecture in RS, with increased proximal and decreased distal interactions. At the compartment scale, the interaction between B compartments was strengthened in DLBCL cells, while topologically associating domains (TADs) in DLBCL had elevated intra-TAD and reduced inter-TAD contacts. Differentially expressed genes at TAD borders between CLL and DLBCL cells highlighted an enrichment of cAMP-mediated signalling. To substantiate the functional relevance of ATF1 and CAP1, the genes involve in cAMP-mediated signalling, in the context of cell proliferation, we have performed gain- and loss-of-function experiments in relevant cell lines. Collectively, integrated scRNA-seq and Hi-C data suggest that chromatin reorganization and altered cAMP signalling drive RS transformation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"15"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030261","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":"ROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2.","authors":"Dan Li, Wenjie Zhang, Ruiheng Wang, Shufeng Xie, Yixin Wang, Wanxin Guo, Zixuan Huang, Chaoqun Lu, Liang Shan, Han Liu, Lifang Ma, Xumin Hou, Zhenshu Xu, Jiayi Wang","doi":"10.1186/s40364-025-00730-0","DOIUrl":"10.1186/s40364-025-00730-0","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer, particularly non-small cell lung cancer (NSCLC), has high recurrence rates and remains a leading cause of cancer-related death, despite recent advances in its treatment. Emerging therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown promise but face significant challenges in targeting solid tumors. This study investigated the potential of combining receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeting CAR-T cells with ferroptosis inducers to promote ferroptosis of tumor cells and enhance anti-tumor efficacy.</p><p><strong>Methods: </strong>RNA-seq data and immunofluorescence analysis of relapsed NSCLC patient samples were used to explore ROR1 expression. In addition, ROR1-targeting CAR-T cells were developed to assess cytotoxic activity against ROR1⁺ tumor cells, and the effect of cytokine stimulation on their efficacy was evaluated. Lipidomics, immunofluorescent histochemistry, and western blotting were used to explore the observed effects. Ferroptosis indicators, including levels of reactive oxygen species, were used to detect the combined effect of CAR-T cells and ferroptosis-inducing drugs. Finally, tumor-bearing mice were used to validate the in vivo efficacy of the combination therapy strategy.</p><p><strong>Results: </strong>Tumor cells treated with ferroptosis inducers showed increased sensitivity to Interferon gamma (IFN-γ) secreted by ROR1 CAR-T cells. Furthermore, ROR1 CAR-T cells enhanced the production of phosphatidylcholine with diacyl-polyunsaturated fatty acid tails (PC-PUFA2) by working in tandem with IFN-γ. This enhancement promoted the expression of acyl-CoA synthetase long chain family member 4 (ACSL4), which in turn strengthened the overall anti-tumor response.</p><p><strong>Conclusions: </strong>Combining ROR1 CAR-T cells with ferroptosis inducers enhanced anti-tumor efficacy in NSCLC by promoting ferroptosis through increased lipid peroxidation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"17"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030315","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}