{"title":"Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.","authors":"Wei Zhang, Miao Zeng, Yisheng Li, Li Yu","doi":"10.1186/s40364-024-00617-6","DOIUrl":"10.1186/s40364-024-00617-6","url":null,"abstract":"<p><p>Adoptive cell therapies (ACTs) have revolutionized cancer immunotherapy, prompting exploration into their application against oncoviruses. Oncoviruses such as human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Epstein-Barr virus (EBV) contribute significantly (12-25%) to human malignancies through direct or indirect oncogenic mechanisms. These viruses persistently or latently infect cells, disrupt cellular homeostasis and pathways, challenging current antiviral treatment paradigms. Moreover, viral infections pose additional risks in the setting of long-term cancer therapy and lead to morbidity and mortality. Virally encoded oncoproteins, which are tumor-restricted, immunologically foreign, and even uniformly expressed, represent promising targets for patient-tailored ACTs. This review elucidates the rationale for leveraging viral antigen-specific ACTs in combating viral-associated malignancies. On this basis, ongoing preclinical studies consolidate our understanding of harnessing ACTs against viral malignancies, underscoring their potential to eradicate viruses implicated in cancer progression. Furthermore, we scrutinize the current landscape of clinical trials focusing on virus-specific ACTs and discuss their implications for therapeutic advancement.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793999","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 targeting cancer-associated fibroblasts through single-cell spatial transcriptomic sequencing.","authors":"Pin Lyu, Xiaoming Gu, Fuqi Wang, Haifeng Sun, Quanbo Zhou, Shuaixi Yang, Weitang Yuan","doi":"10.1186/s40364-024-00622-9","DOIUrl":"10.1186/s40364-024-00622-9","url":null,"abstract":"<p><p>Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment and are related to tumor proliferation, metastasis, relapse, and drug resistance. With the development of sequencing technologies, single-cell RNA sequencing has become a popular method for identifying CAFs in the tumor microenvironment. Whereas the drawbacks of CAFs, such as the lack of a spatial landscape, still exist, recent research has utilized spatial transcriptomics combined with single-cell RNA sequencing to address this issue. These multiomics analyses can resolve the single-cell resolution problem in spatial transcriptomics. In this review, we summarized the recent literature regarding the targeting of CAFs to address drug resistance, angiogenesis, metabolic reprogramming and metastasis in tumor tissue.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793997","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}
Zhi-Yu Duan, Chun Zhang, Xiang-Mei Chen, Guang-Yan Cai
{"title":"Blood and urine biomarkers of disease progression in IgA nephropathy.","authors":"Zhi-Yu Duan, Chun Zhang, Xiang-Mei Chen, Guang-Yan Cai","doi":"10.1186/s40364-024-00619-4","DOIUrl":"10.1186/s40364-024-00619-4","url":null,"abstract":"<p><p>The prognosis of patients with IgA nephropathy (IgAN) is variable but overall not good. Almost all patients with IgAN are at risk of developing end-stage renal disease within their expected lifetime. The models presently available for prediction of the risk of progression of IgAN, including the International IgA Nephropathy Prediction Tool, consist of traditional clinical, pathological, and therapeutic indicators. Finding biomarkers to improve the existing risk prediction models or replace pathological indicators is important for clinical practice. Many studies have attempted to identify biomarkers for prediction of progression of IgAN, such as galactose-deficient IgA1, complement, a spectrum of protein biomarkers, non-coding RNA, and shedding cells. This article reviews the biomarkers of progression of IgAN identified in recent years, with a focus on those with clinical value, in particular the combination of multiple biomarkers into a biomarker spectrum. Future research should focus on establishing a model based primarily on biomarkers that can predict progression of IgAN and testing it in various patient cohorts.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793998","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}
Hengrui Liu, Jieling Weng, Christopher L-H Huang, Antony P Jackson
{"title":"Voltage-gated sodium channels in cancers.","authors":"Hengrui Liu, Jieling Weng, Christopher L-H Huang, Antony P Jackson","doi":"10.1186/s40364-024-00620-x","DOIUrl":"10.1186/s40364-024-00620-x","url":null,"abstract":"<p><p>Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from \"non-excitable\" tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory β-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768044","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}
Maria L. Cagigas, Giovanni Fiorito, Beatrice Bertozzi, Andrius Masedunskas, Edda Cava, Francesco Spelta, Nicola Veronese, Valeria Tosti, Gayathiri Rajakumar, Tiana Pelaia, Arnold D. Bullock, Robert S. Figenshau, Gerald L. Andriole, Luigi Fontana
{"title":"Effects of protein restriction on insulin-like growth factor (IGF)-1 in men with prostate cancer: results from a randomized clinical trial","authors":"Maria L. Cagigas, Giovanni Fiorito, Beatrice Bertozzi, Andrius Masedunskas, Edda Cava, Francesco Spelta, Nicola Veronese, Valeria Tosti, Gayathiri Rajakumar, Tiana Pelaia, Arnold D. Bullock, Robert S. Figenshau, Gerald L. Andriole, Luigi Fontana","doi":"10.1186/s40364-024-00613-w","DOIUrl":"https://doi.org/10.1186/s40364-024-00613-w","url":null,"abstract":"Insulin-like growth factor (IGF)-1 and its binding proteins are important in cancer growth, especially in prostate cancer. Observational studies suggest that protein restriction can lower IGF-1 levels. However, it is unclear whether an isocaloric protein-restricted diet affects IGF-1 and IGFBPs in men with prostate cancer. In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded end-point trial, 38 consenting overweight (BMI 30.5 ± 5.5 kg/m2) men with localized prostate cancer, aged 43–72 years, were randomized (1:1) with permuted blocks to 4–6 weeks of customized isocaloric PR diets (0.8 g protein/kg lean body mass) or their usual diet. Biomarkers influencing cancer biology, including serum IGF-1 and its binding proteins were measured longitudinally. Contrary to our hypothesis, feeding individuals an isocaloric protein-restricted diet did not result in a significant reduction in serum IGF-1. Moreover, there was no observed increase in serum IGFBP-1 or IGFBP-3 concentration. These findings demonstrate that protein restriction without calorie restriction does not reduce serum IGF-1 concentration or increase IGFBP-1 and IGFBP-3 in men with localized prostate cancer. Further research is needed to identify dietary interventions for safely and effectively reducing IGF-1 in this patient group.","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141737881","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}
Ashley N Anderson, Patrick Conley, Christopher D Klocke, Sidharth K Sengupta, Amara Pang, Hannah C Farley, Abigail R Gillingham, Aubrey D Dawson, Yichen Fan, Jocelyn A Jones, Summer L Gibbs, Alison H Skalet, Guanming Wu, Melissa H Wong
{"title":"Detection of neoplastic-immune hybrid cells with metastatic properties in uveal melanoma.","authors":"Ashley N Anderson, Patrick Conley, Christopher D Klocke, Sidharth K Sengupta, Amara Pang, Hannah C Farley, Abigail R Gillingham, Aubrey D Dawson, Yichen Fan, Jocelyn A Jones, Summer L Gibbs, Alison H Skalet, Guanming Wu, Melissa H Wong","doi":"10.1186/s40364-024-00609-6","DOIUrl":"10.1186/s40364-024-00609-6","url":null,"abstract":"<p><strong>Background: </strong>Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression.</p><p><strong>Methods: </strong>To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells.</p><p><strong>Results: </strong>Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1.</p><p><strong>Conclusion: </strong>These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728296","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}
Mehdi Bakhtiyaridovvombaygi, Somayeh Yazdanparast, Setare Kheyrandish, Seyed Mehrab Safdari, Fateme Amiri Samani, Mahsa Sohani, Akram Sadat Jaafarian, Fateme Damirchiloo, Amirhossein Izadpanah, Sahar Parkhideh, Fatemeh Mikanik, Elham Roshandel, Abbas Hajifathali, Ahmad Gharehbaghian
{"title":"Harnessing natural killer cells for refractory/relapsed non-Hodgkin lymphoma: biological roles, clinical trials, and future prospective.","authors":"Mehdi Bakhtiyaridovvombaygi, Somayeh Yazdanparast, Setare Kheyrandish, Seyed Mehrab Safdari, Fateme Amiri Samani, Mahsa Sohani, Akram Sadat Jaafarian, Fateme Damirchiloo, Amirhossein Izadpanah, Sahar Parkhideh, Fatemeh Mikanik, Elham Roshandel, Abbas Hajifathali, Ahmad Gharehbaghian","doi":"10.1186/s40364-024-00610-z","DOIUrl":"10.1186/s40364-024-00610-z","url":null,"abstract":"<p><p>Non-Hodgkin lymphomas (NHLs) are heterogeneous and are among the most common hematological malignancies worldwide. Despite the advances in the treatment of patients with NHLs, relapse or resistance to treatment is anticipated in several patients. Therefore, novel therapeutic approaches are needed. Recently, natural killer (NK) cell-based immunotherapy alone or in combination with monoclonal antibodies, chimeric antigen receptors, or bispecific killer engagers have been applied in many investigations for NHL treatment. The functional defects of NK cells and the ability of cancerous cells to escape NK cell-mediated cytotoxicity within the tumor microenvironment of NHLs, as well as the beneficial results from previous studies in the context of NK cell-based immunotherapy in NHLs, direct our attention to this therapeutic strategy. This review aims to summarize clinical studies focusing on the applications of NK cells in the immunotherapy of patients with NHL.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635733","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 involvement of krüppel-like transcription factor 2 in megakaryocytic differentiation induction by phorbol 12-myrestrat 13-acetate.","authors":"Zhen Wang, Zhongwen Liu, Pan Zhou, Xiaona Niu, Zhengdao Sun, Huan He, Zunmin Zhu","doi":"10.1186/s40364-024-00614-9","DOIUrl":"10.1186/s40364-024-00614-9","url":null,"abstract":"<p><strong>Background: </strong>Megakaryocytic differentiation is a complicated process regulated by a series of transcription factors in a context- and stage-dependent manner. Recent studies have suggested that krüppel-like transcription factor 2 (KLF2) is involved in the control of embryonic erythroid precursor cell differentiation and maturation. However, the function and mechanism of KLF2 in regulating megakaryocytic differentiation remain unclear.</p><p><strong>Methods: </strong>The expression patterns of krüppel-like transcription factors (KLFs) during megakaryocytic differentiation were identified from public databases. Phorbol 12-myristate 13-acetate (PMA) treatment of the myeloid-erythroid-leukemic cell lines K562 and HEL were used as cellular megakaryocytic differentiation models. A lentiviral transduction system was utilized to achieve the goal of amplifying or reducing KLF2. The expression of KLF2 was examined using real-time PCR and western blot. The impact of KLF2 on the megakaryocytic differentiation of K562 cells was examined by flow cytometry, Giemsa staining, Phalloidin staining and western blot. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) technologies were used to identify the KLF2-regulated targets.</p><p><strong>Results: </strong>KLF2 is increased in the maturation process of megakaryocytes. KLF2 overexpression accelerated the PMA-induced megakaryocytic differentiation, as reflected by an increased percentage of CD41/CD61 cells, an increased number of polyploid cells, and an elevated expression of P21 and P27. KLF2 knockdown exhibited the opposite results, indicating that KLF2 knockdown suppressed the megakaryocytic differentiation. Further, combination of the RNA-seq and ChIP-seq results suggested that chimerin 1 (CHN1) and potassium voltage-gated channel subfamily Q member 5 (KCNQ5) may be target genes regulated of KLF2. Both CHN1 and KCNQ5 knockdown could block the megakaryocytic differentiation to some content.</p><p><strong>Conclusion: </strong>This study implicated a regulatory role of KLF2 in megakaryocytic differentiation, which may suggest KLF2 as a target for illness with abnormal megakaryocytic differentiation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629230","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}