Biomarker Research最新文献

{"title":"Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.","authors":"Fei Du, Guojun Wang, Qian Dai, Jiang Huang, Junxin Li, Congxing Liu, Ke Du, Hua Tian, Qiwei Deng, Longxiang Xie, Xin Zhao, Qimin Zhang, Lan Yang, Yaling Li, Zhigui Wu, Zhuo Zhang","doi":"10.1186/s40364-025-00748-4","DOIUrl":"10.1186/s40364-025-00748-4","url":null,"abstract":"<p><p>The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in cancer treatment over recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone of tumor immunotherapy, have emerged as one of the most promising advancements in cancer treatment. Although ICIs, such as CTLA-4 and PD-1/PD-L1 inhibitors, have demonstrated clinical efficacy, their therapeutic impact remains suboptimal due to patient-specific variability and tumor immune resistance. Cell death is a fundamental process for maintaining tissue homeostasis and function. Recent research highlights that the combination of induced regulatory cell death (RCD) and ICIs can substantially enhance anti-tumor responses across multiple cancer types. In cells exhibiting high levels of recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers a programmed cell death (PCD) pathway characterized by disulfide bond formation and REDOX (reduction-oxidation) reactions, termed \"disulfidptosis.\" Studies suggest that disulfidptosis plays a critical role in the therapeutic efficacy of SLC7A11^high cancers. Therefore, to investigate the potential synergy between disulfidptosis and ICIs, this study will explore the mechanisms of both processes in tumor progression, with the goal of enhancing the anti-tumor immune response of ICIs by targeting the intracellular disulfidptosis pathway.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"35"},"PeriodicalIF":9.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517278","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 multi-omics analysis identifies SPP1⁺ macrophages as key drivers of ferroptosis-mediated fibrosis in ligamentum flavum hypertrophy.","authors":"Chengshuo Fei, Yanlin Chen, Ruiqian Tan, Xinxing Yang, Guanda Wu, Chenglong Li, Jiawei Shi, Shiyong Le, Wenjie Yang, Jiajia Xu, Liang Wang, Zhongmin Zhang","doi":"10.1186/s40364-025-00746-6","DOIUrl":"10.1186/s40364-025-00746-6","url":null,"abstract":"<p><strong>Background: </strong>Ligamentum flavum hypertrophy (LFH) is a primary contributor to lumbar spinal stenosis. However, a thorough understanding of the cellular and molecular mechanisms driving LFH fibrotic progression remains incomplete.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was performed to construct the single-cell map of human ligamentum flavum (LF) samples. An integrated multi-omics approach, encompassing scRNA-seq, bulk RNA sequencing (bulk RNA-seq), and Mendelian randomization (MR), was applied to conduct comprehensive functional analysis. Clinical tissue specimens and animal models were employed to further confirm the multi-omics findings.</p><p><strong>Results: </strong>ScRNA-seq provided a single-cell level view of the fibrotic microenvironment in LF, revealing significantly increased proportions of fibroblasts, myofibroblasts, and macrophages in LFH. Using transmission electron microscopy, single-cell gene set scoring, and MR analysis, ferroptosis was identified as a critical risk factor and pathway within LFH. Subcluster analysis of fibroblasts revealed functional heterogeneity among distinct subpopulations, highlighting the functional characteristics and the metabolic dynamics of fibroblast with a high ferroptosis score (High Ferro-score FB). The quantification of gene expression at single-cell level revealed that ferroptosis increased along with fibrosis in LFH specimens, a finding further validated in both human and mice tissue sections. Consistently, bulk RNA-seq confirmed increased proportions of fibroblasts and macrophages in LFH specimens, underscoring a strong correlation between these cell types through Spearman correlation analysis. Notably, subcluster analysis of the mononuclear phagocytes identified a specific subset of SPP1⁺ macrophages (SPP1⁺ Mac) enriched in LFH, which exhibited activation of fibrosis and ferroptosis-related metabolic pathways. Cell-cell communication analysis highlighted that SPP1⁺ Mac exhibited the strongest outgoing and incoming interactions among mononuclear phagocytes in the LFH microenvironment. Ligand-receptor analysis further revealed that the SPP1-CD44 axis could serve as a key mediator regulating the activity of High Ferro-score FB. Multiplex immunofluorescence confirmed substantial Collagen I deposition and reduced Ferritin Light Chain expression in regions with SPP1-CD44 co-localization in LFH specimens.</p><p><strong>Conclusions: </strong>Our findings indicated that SPP1⁺ Mac may contribute to LFH fibrosis by regulating ferroptosis in High Ferro-score FB through the SPP1-CD44 axis. This study enhances our understanding of the cellular and molecular mechanisms underlying LFH progression, potentially improving early diagnostic strategies and identifying new therapeutic targets.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"33"},"PeriodicalIF":9.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505953","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":"Toll-like receptor 3: a double-edged sword.","authors":"Marvin L Hsieh, Daisuke Nishizaki, Jacob J Adashek, Shumei Kato, Razelle Kurzrock","doi":"10.1186/s40364-025-00739-5","DOIUrl":"10.1186/s40364-025-00739-5","url":null,"abstract":"<p><p>The discovery of Toll-like receptors (TLRs) and their role in dendritic cells earned the Nobel Prize for 2011 because TLRs profoundly enhanced our understanding of the immune system. Specifically, TLR3 is located within the endosomal compartments of dendritic cells and plays a crucial role in the immune response by acting as a pattern recognition receptor that detects both exogenous (viral) and endogenous (mammalian) double-stranded RNA. However, TLR3 activation is a double-edged sword in various immune-mediated diseases. On one hand, it can enhance anti-viral defenses and promote pathogen clearance, contributing to host protection. On the other hand, excessive or dysregulated TLR3 signaling can lead to chronic inflammation and tissue damage, exacerbating conditions such as autoimmune diseases, chronic viral infections, and cancer. In cancer, TLR3 expression has been linked to both favorable and poor prognoses, though the underlying mechanisms remain unclear. Recent clinical and preclinical advances have explored the use of TLR3 agonists in cancer immunotherapy, attempting to capitalize on their potential to enhance anti-tumor responses. The dual role of TLR3 highlights its complexity as a therapeutic target, necessitating careful modulation to maximize its protective effects while minimizing potential pathological consequences. In this review, we explore the intricate roles of TLR3 in immune responses across different disease contexts, including cancer, infections, autoimmune disorders, and allergies, highlighting both its protective and detrimental effects in these disorders, as well as progress in developing TLR3 agonists as part of the immunotherapy landscape.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"32"},"PeriodicalIF":9.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484712","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":"Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics.","authors":"Andréa Witz, Julie Dardare, Margaux Betz, Cassandra Michel, Marie Husson, Pauline Gilson, Jean-Louis Merlin, Alexandre Harlé","doi":"10.1186/s40364-025-00740-y","DOIUrl":"10.1186/s40364-025-00740-y","url":null,"abstract":"<p><p>The use of poly(ADP-ribose) polymerase inhibitors (PARPi) revolutionized the treatment of BRCA-mutated cancers. Identifying patients exhibiting homologous recombination deficiency (HRD) has been proved useful to predict PARPi efficacy. However, obtaining HRD status remains an arduous task due to its evolution over the time. This causes HRD status to become obsolete when obtained from genomic scars, rendering PARPi ineffective for these patients. Only two HRD tests are currently FDA-approved, both based on genomic scars detection and BRCA mutations testing. Nevertheless, new technologies for obtaining an increasingly reliable HRD status continue to evolve. Application of these tests in clinical practice is an additional challenge due to the need for lower costs and shorter time to results delay.In this review, we describe the currently available methods for HRD testing, including the methodologies and corresponding tests for assessing HRD status, and discuss the clinical routine application of these tests and their technical validation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"31"},"PeriodicalIF":9.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477253","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":"Multiple regulatory events contribute to a widespread circular RNA downregulation in precancer and early stage of colorectal cancer development.","authors":"Alessandro Camandona, Amedeo Gagliardi, Nicola Licheri, Sonia Tarallo, Giulia Francescato, Eva Budinska, Martina Carnogurska, Barbora Zwinsová, Barbara Martinoglio, Lorenzo Franchitti, Gaetano Gallo, Santina Cutrupi, Michele De Bortoli, Barbara Pardini, Alessio Naccarati, Giulio Ferrero","doi":"10.1186/s40364-025-00744-8","DOIUrl":"10.1186/s40364-025-00744-8","url":null,"abstract":"<p><strong>Background: </strong>Early detection of colorectal cancer (CRC) significantly improves its management and patients' survival. Circular RNAs (circRNAs) are peculiar covalently closed transcripts involved in gene expression modulation whose dysregulation has been extensively reported in CRC cells. However, little is known about their alterations in the early phases of colorectal carcinogenesis.</p><p><strong>Methods: </strong>In this study, we performed an integrative analysis of circRNA profiles in RNA-sequencing (RNA-Seq) data of 96 colorectal cancers, 27 adenomas, and matched adjacent mucosa tissues. We also investigated the levels of cognate linear transcripts and those of regulating RNA-binding proteins (RBPs). Levels of circRNA-interacting microRNAs (miRNAs) were explored by integrating data of small RNA-Seq performed on the same samples.</p><p><strong>Results: </strong>Our results revealed a significant dysregulation of 34 circRNAs (paired adj. p < 0.05), almost exclusively downregulated in tumor tissues and, prevalently, in early disease stages. This downregulation was associated with decreased expression of circRNA host genes and those encoding for RBPs involved in circRNA biogenesis, including NOVA1, RBMS3, and MBNL1. Guilt-by-association analysis showed that dysregulated circRNAs correlated with increased predicted activity of cell proliferation, DNA repair, and c-Myc signaling pathways. Functional analysis showed interactions among dysregulated circRNAs, RBPs, and miRNAs, which were supported by significant correlations among their expression levels. Findings were validated in independent cohorts and public datasets, and the downregulation of circLPAR1(2,3) and circLINC00632(5) was validated by ddPCR.</p><p><strong>Conclusions: </strong>These results support that multiple altered regulatory mechanisms may contribute to the reduction of circRNA levels that characterize early colorectal carcinogenesis.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"30"},"PeriodicalIF":9.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470016","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":"Correction: MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer.","authors":"Xin-Yi Sui, Shuo-Wen Cao, Xiao-Qing Song, Xi-Yu Liu, Chao Chen, Qingya Yan, Zhi-Qing Wang, Wen-Juan Zhang, Lin-Xiaoxi Ma, Xi Jin, Ding Ma, Yi Xiao, Song-Yang Wu, Ying Xu, Zhi-Ming Shao, Lei Fan","doi":"10.1186/s40364-025-00743-9","DOIUrl":"10.1186/s40364-025-00743-9","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"29"},"PeriodicalIF":9.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416103","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":"Unveiling the potential of CLL-1: a promising target for AML therapy.","authors":"Hamed Soleimani Samarkhazan, Sara Zehtabcheh, Hamideh Rahmani Seraji, Safedin H Beqaj, Shamim Tayefeh, Mohammad Hossein Mohammadi, Mojtaba Aghaei","doi":"10.1186/s40364-025-00738-6","DOIUrl":"10.1186/s40364-025-00738-6","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) remains a formidable blood cancer, despite recent advances in treatment. A significant challenge persists in improving patient outcomes, particularly in addressing relapse and treatment resistance. Identifying new therapeutic targets is critical for advancing AML therapy. C-type lectin-like molecule-1 (CLL-1) has emerged as a promising therapeutic target in AML. This cell surface receptor is highly expressed on AML blasts and demonstrates stable expression throughout disease progression. CLL-1's consistent presence makes it an ideal candidate for monitoring minimal residual disease (MRD), which is a critical indicator for predicting relapse. Beyond its utility as a diagnostic marker, CLL-1 offers exciting potential in the development of immunotherapies. Emerging strategies, such as CAR-T-cell therapy and antibody-drug conjugates (ADCs), are being investigated to leverage the immune system against CLL-1-expressing AML cells. This review examines the structure, function, and expression patterns of CLL-1 in AML and other hematologic malignancies, providing insights into its role in disease pathogenesis and treatment potential. Exploring CLL-1 as a target for diagnosis, MRD monitoring, and immunotherapy opens new avenues for AML treatment. A deeper understanding of its relationship with AML pathogenesis will aid in the development of targeted therapies, offering hope for improved patient outcomes in the future.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"28"},"PeriodicalIF":9.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411499","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 platelets in cancer: from their influence on tumor progression to their potential use in liquid biopsy.","authors":"Miguel Morales-Pacheco, Miguel Valenzuela-Mayen, Angel M Gonzalez-Alatriste, Gretel Mendoza-Almanza, Sergio A Cortés-Ramírez, Alberto Losada-García, Griselda Rodríguez-Martínez, Imelda González-Ramírez, Vilma Maldonado-Lagunas, Karla Vazquez-Santillan, Vanessa González-Covarrubias, Carlos Pérez-Plasencia, Mauricio Rodríguez-Dorantes","doi":"10.1186/s40364-025-00742-w","DOIUrl":"10.1186/s40364-025-00742-w","url":null,"abstract":"<p><p>Platelets, anucleate blood cells essential for hemostasis, are increasingly recognized for their role in cancer, challenging the traditional notion of their sole involvement in blood coagulation. It has been demonstrated that platelets establish bidirectional communication with tumor cells, contributing to tumor progression and metastasis through diverse molecular mechanisms such as modulation of proliferation, angiogenesis, epithelial-mesenchymal transition, resistance to anoikis, immune evasion, extravasation, chemoresistance, among other processes. Reciprocally, cancer significantly alters platelets in their count and composition, including mRNA, non-coding RNA, proteins, and lipids, product of both internal synthesis and the uptake of tumor-derived molecules. This phenomenon gives rise to tumor-educated platelets (TEPs), which are emerging as promising tools for the development of liquid biopsies. In this review, we provide a detailed overview of the dynamic roles of platelets in tumor development and progression as well as their use in diagnosis and prognosis. We also provide our view on current limitations, challenges and future research areas, including the need to design more efficient strategies for their isolation and analysis, as well as the validation of their sensitivity and specificity through large-scale and rigorous clinical trials. This research will not only enable the evaluation of their clinical viability but could also open new opportunities to enhance diagnostic accuracy and develop personalized treatments in oncology.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"27"},"PeriodicalIF":9.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11818056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400749","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":"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}