Biomarker Research最新文献

{"title":"Single-cell and bulk RNA-seq unveils the immune infiltration landscape associated with cuproptosis in cerebral cavernous malformations.","authors":"Chengwei Chen, Yuting Bao, Sihan Ju, Conglin Jiang, Xiang Zou, Xin Zhang, Liang Chen","doi":"10.1186/s40364-024-00603-y","DOIUrl":"10.1186/s40364-024-00603-y","url":null,"abstract":"<p><strong>Background: </strong>Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development.</p><p><strong>Methods: </strong>Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs.</p><p><strong>Results: </strong>Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis.</p><p><strong>Conclusion: </strong>This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes-PFDN4, CEMIP, and BTBD10-may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"57"},"PeriodicalIF":11.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248993","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 and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma","authors":"Liyuan Dai, Guangyu Fan, Tongji Xie, Lin Li, Le Tang, Haizhu Chen, Yuankai Shi, Xiaohong Han","doi":"10.1186/s40364-024-00605-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00605-w","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077–2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207–5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p < 0.05) in DLBCL. Immunohistochemical validation of glycolysis markers (STMN1, ENO1, PKM, and CDK1) and multiple immunofluorescence validation of IFN_TAMs underscored their prognostic value (p < 0.05) in DLBCL. This study underscores the significance of glycolysis in tumor progression and modulation of the immune microenvironment. The identified glycolysis genes and IFN_TAMs represent potential prognostic markers and therapeutic targets in DLBCL.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"313 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141259960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer.","authors":"Chengpei Zhu, Yunchao Wang, Ruijuan Zhu, Shanshan Wang, Jingnan Xue, Dongya Zhang, Zhou Lan, Chenchen Zhang, Yajun Liang, Nan Zhang, Ziyu Xun, Longhao Zhang, Cong Ning, Xu Yang, Jiashuo Chao, Junyu Long, Xiaobo Yang, Hanping Wang, Xinting Sang, Xianzhi Jiang, Haitao Zhao","doi":"10.1186/s40364-024-00607-8","DOIUrl":"10.1186/s40364-024-00607-8","url":null,"abstract":"<p><strong>Background: </strong>Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.</p><p><strong>Methods: </strong>This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored.</p><p><strong>Results: </strong>Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy.</p><p><strong>Conclusions: </strong>Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"56"},"PeriodicalIF":11.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238827","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 and spatial transcriptomics reveal alterations in trophoblasts at invasion sites and disturbed myometrial immune microenvironment in placenta accreta spectrum disorders.","authors":"Kaiyuan Ji, Yunshan Chen, Xiuyu Pan, Lina Chen, Xiaodi Wang, Bolun Wen, Junjie Bao, Junmin Zhong, Zi Lv, Zheng Zheng, Huishu Liu","doi":"10.1186/s40364-024-00598-6","DOIUrl":"10.1186/s40364-024-00598-6","url":null,"abstract":"<p><strong>Background: </strong>Placenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS involve a complex interplay of various cell types and molecular pathways. Despite its significance, both the characteristics and intricate mechanisms of this condition remain poorly understood.</p><p><strong>Methods: </strong>Spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), were performed on the tissue samples from four PAS patients, including invasive tissues (ST, n = 3; scRNA-seq, n = 4), non-invasive normal placenta samples (ST, n = 1; scRNA-seq, n = 2). Three healthy term pregnant women provided normal myometrium samples (ST, n = 1; scRNA-seq, n = 2). ST analysis characterized the spatial expression landscape, and scRNA-seq was used to identify specific cellular components in PAS. Immunofluorescence staining was conducted to validate the findings.</p><p><strong>Results: </strong>ST slices distinctly showed the myometrium in PAS was invaded by three subpopulations of trophoblast cells, extravillous trophoblast cells, cytotrophoblasts, and syncytiotrophoblasts, especially extravillous trophoblast cells. The pathways enriched by genes in trophoblasts, smooth muscle cells (SMC), and immune cells of PAS were mainly associated with immune and inflammation. We identified elevated expression of the angiogenesis-stimulating gene PTK2, alongside the cell proliferation-enhancing gene EGFR, within the trophoblasts of PAS group. Trophoblasts mainly contributed the enhancement of HLA-G and EBI3 signaling, which is crucial in establishing immune escape. Meanwhile, SMC regions in PAS exhibited upregulation of immunomodulatory markers such as CD274, HAVCR2, and IDO1, with CD274 expression experimentally verified to be increased in the invasive SMC areas of the PAS group.</p><p><strong>Conclusions: </strong>This study provided information of cellular composition and spatial organization in PAS at single-cell and spatial level. The dysregulated expression of genes in PAS revealed a complex interplay between enhanced immune escape in trophoblasts and immune tolerance in SMCs during invasion in PAS. These findings will enhance our understanding of PAS pathogenesis for developing potential therapeutic strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"55"},"PeriodicalIF":11.1,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238828","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":"CRISPR/Cas-based CAR-T cells: production and application.","authors":"Ping Song, Qiqi Zhang, Zhiyong Xu, Yueli Shi, Ruirui Jing, Dingcun Luo","doi":"10.1186/s40364-024-00602-z","DOIUrl":"10.1186/s40364-024-00602-z","url":null,"abstract":"<p><p>Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment approach for cancer, autoimmune disease, and heart disease. The integration of CAR into T cells is typically facilitated by retroviral or lentiviral vectors. However, the random insertion of CARs can lead to issues like clonal expansion, oncogenic transformation, variegated transgene expression, and transcriptional silencing. The advent of precise gene editing technology, like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), allows for controlled and precise genome modification, facilitating the translation of CAR-T research to the clinical applications. This review aims to provide a comprehensive analysis of the application of CRISPR gene editing techniques in the context of precise deletion and insertion methodologies, with a specific focus on their potential for enhancing the development and utilization of CAR-T cell therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"54"},"PeriodicalIF":9.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181171","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":"FGL1 and FGL2: emerging regulators of liver health and disease.","authors":"Jiongming Chen, Lei Wu, Yongsheng Li","doi":"10.1186/s40364-024-00601-0","DOIUrl":"10.1186/s40364-024-00601-0","url":null,"abstract":"<p><p>Liver disease is a complex group of diseases with high morbidity and mortality rates, emerging as a major global health concern. Recent studies have highlighted the involvement of fibrinogen-like proteins, specifically fibrinogen-like protein 1 (FGL1) and fibrinogen-like protein 2 (FGL2), in the regulation of various liver diseases. FGL1 plays a crucial role in promoting hepatocyte growth, regulating lipid metabolism, and influencing the tumor microenvironment (TME), contributing significantly to liver repair, non-alcoholic fatty liver disease (NAFLD), and liver cancer. On the other hand, FGL2 is a multifunctional protein known for its role in modulating prothrombin activity and inducing immune tolerance, impacting viral hepatitis, liver fibrosis, hepatocellular carcinoma (HCC), and liver transplantation. Understanding the functions and mechanisms of fibrinogen-like proteins is essential for the development of effective therapeutic approaches for liver diseases. Additionally, FGL1 has demonstrated potential as a disease biomarker in radiation and drug-induced liver injury as well as HCC, while FGL2 shows promise as a biomarker in viral hepatitis and liver transplantation. The expression levels of these molecules offer exciting prospects for disease assessment. This review provides an overview of the structure and roles of FGL1 and FGL2 in different liver conditions, emphasizing the intricate molecular regulatory processes and advancements in targeted therapies. Furthermore, it explores the potential benefits and challenges of targeting FGL1 and FGL2 for liver disease treatment and the prospects of fibrinogen-like proteins as biomarkers for liver disease, offering insights for future research in this field.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"53"},"PeriodicalIF":11.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181204","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":"PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals.","authors":"Ji Young Kim, Ji Hye Shin, Mi-Jeong Kim, Bongkum Choi, Yeeun Kang, Jimin Choi, Seo Hyun Kim, Dohee Kwan, Duk-Hwan Kim, Eunyoung Chun, Ki-Young Lee","doi":"10.1186/s40364-024-00604-x","DOIUrl":"10.1186/s40364-024-00604-x","url":null,"abstract":"<p><p>Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγ^null) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"52"},"PeriodicalIF":11.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181206","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 war between the immune system and the tumor - using immune biomarkers as tracers.","authors":"Kai Yang, Rongrong Lu, Jie Mei, Kai Cao, Tianyu Zeng, Yijia Hua, Xiang Huang, Wei Li, Yongmei Yin","doi":"10.1186/s40364-024-00599-5","DOIUrl":"10.1186/s40364-024-00599-5","url":null,"abstract":"<p><p>Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"51"},"PeriodicalIF":11.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181219","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":"Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection.","authors":"Lorena Pérez-Carrillo, Isaac Giménez-Escamilla, Irene González-Torrent, Marta Delgado-Arija, Ignacio Sánchez-Lázaro, María García-Manzanares, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, Esther Roselló-Lletí","doi":"10.1186/s40364-024-00590-0","DOIUrl":"10.1186/s40364-024-00590-0","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"49"},"PeriodicalIF":11.1,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913106","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":"CD19-immunoPET for noninvasive visualization of CD19 expression in B-cell lymphoma patients.","authors":"Dominik Sonanini, Johannes Schwenck, Simone Blaess, Julia Schmitt, Andreas Maurer, Walter Ehrlichmann, Malte Ritter, Julia Skokowa, Manfred Kneilling, Gundram Jung, Falko Fend, Simon Krost, Christian M Seitz, Peter Lang, Gerald Reischl, Rupert Handgretinger, Christian la Fougère, Bernd J Pichler","doi":"10.1186/s40364-024-00595-9","DOIUrl":"10.1186/s40364-024-00595-9","url":null,"abstract":"<p><p>Cell- and antibody-based CD19-directed therapies have demonstrated great potential for treating B-cell non-Hodgkin lymphoma (B-NHL). However, all these approaches suffer from limited response rates and considerable toxicity. Until now, therapy decisions have been routinely based on histopathological CD19 staining of a single lesion at initial diagnosis or relapse, disregarding heterogeneity and temporal alterations in antigen expression. To visualize in vivo CD19 expression noninvasively, we radiolabeled anti-human CD19 monoclonal antibodies with copper-64 (⁶⁴Cu-αCD19) for positron emission tomography (CD19-immunoPET). ⁶⁴Cu-αCD19 specifically bound to subcutaneous Daudi xenograft mouse models in vivo. Importantly, ⁶⁴Cu-αCD19 did not affect the anti-lymphoma cytotoxicity of CD19 CAR-T cells in vitro. Following our preclinical validation, ⁶⁴Cu-αCD19 was injected into four patients with follicular lymphoma, diffuse large B-cell lymphoma or mantle zone lymphoma. We observed varying ⁶⁴Cu-αCD19 PET uptake patterns at different lymphoma sites, both within and among patients, correlating with ex vivo immunohistochemical CD19 expression. Moreover, one patient exhibited enhanced uptake in the spleen compared to that in patients with prior B-cell-depleting therapy, indicating that ⁶⁴Cu-αCD19 is applicable for identifying B-cell-rich organs. In conclusion, we demonstrated the specific targeting and visualization of CD19⁺ B-NHL in mice and humans by CD19-immunoPET. The intra- and interindividual heterogeneous ⁶⁴Cu-αCD19 uptake patterns of lymphoma lesions indicate variability in CD19 expression, suggesting the potential of CD19-immunoPET as a novel tool to guide CD19-directed therapies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"12 1","pages":"50"},"PeriodicalIF":11.1,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913039","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}