BioFactors最新文献

{"title":"HPV Infection Drives CXCL8+ Neutrophil-Mediated Immune Suppression in Cervical Cancer","authors":"Miaomiao Liu,&nbsp;Lina Zhang,&nbsp;Yanan Fan,&nbsp;Lina Han,&nbsp;Lei Tian,&nbsp;Lili Peng,&nbsp;Liya He,&nbsp;Qiaofang Li,&nbsp;Xiaolu Yan,&nbsp;Ting Shen","doi":"10.1002/biof.70131","DOIUrl":"10.1002/biof.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Persistent HPV infection is a major risk factor for cervical cancer, but the immune mechanisms behind HPV-induced tumor progression are not fully understood. Neutrophils may play a key role in immune remodeling and evasion within the HPV-infected tumor microenvironment. We integrated 31 cervical samples (including HPV-infected and non-infected normal, tumor, and HSIL tissues) to construct a single-cell atlas of 141,785 cells. Neutrophil heterogeneity, cell–cell communication, and immunosuppressive programs were systematically analyzed. Transcriptomic findings were validated via immunohistochemistry, immunofluorescence, and Mendelian randomization (MR). HPV infection dramatically remodeled the immune landscape, inducing robust neutrophil and plasma cell infiltration while reducing T cell abundance. Neutrophils in HPV+ tissues were terminally differentiated and displayed a distinct CXCL8⁺ phenotype. These CXCL8⁺ neutrophils were identified as late-stage, transcriptionally defined low-plasticity state enriched with immunosuppressive genes (e.g., SPP1, VEGFA). They exhibited enhanced interactions with T cell subsets, particularly regulatory and cytotoxic T cells, via ligands like CXCL16 and APOE, suggesting direct immunosuppressive crosstalk. MR analysis indicated a causal role for CXCL8 in cervical cancer, and spatial protein assays confirmed elevated CXCL8 and its receptor CSF3R in HPV+ tumors. HPV infection expands immunosuppressive CXCL8⁺ neutrophils that modulate T cell activity and promote immune escape. CXCL8 is identified as a causal factor and potential therapeutic target in HPV-driven cervical cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caenorhabditis elegans and Drosophila melanogaster as Model Organisms in Biofactor Research","authors":"Kai Lüersen,&nbsp;Thomas Roeder,&nbsp;Gerald Rimbach","doi":"10.1002/biof.70127","DOIUrl":"10.1002/biof.70127","url":null,"abstract":"<p>Model organisms play a central role in advancing our understanding of human nutrition and physiology. This narrative review highlights the unique advantages of the invertebrate models <i>Caenorhabditis elegans</i> and <i>Drosophila melanogaster</i> for studying biofactors—diet-derived compounds that modulate biological functions. Both models offer powerful genetic toolkits, short life cycles, and cost-effective maintenance, enabling high-throughput and mechanistic investigations. Particular emphasis is placed on the availability of chemically defined diets, which allow precise manipulation of nutrient and biofactor composition. These features make <i>C. elegans</i> and <i>D. melanogaster</i> invaluable systems for dissecting the essentiality, bioavailability, and physiological impact of individual biofactors as illustrated by selected recent studies. Being ethically less problematic substitutes for mammalian models, both invertebrate models offer the possibility of closing the gap that often exists between in vitro and cell culture studies on the one hand and in vivo evaluation in animal experiments in laboratory rodents on the other. By integrating these model systems into experimental research, we can gain critical insights into biofactor-gene interactions and the molecular mechanisms underlying their health-promoting properties.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Multi-Omics Analysis Reveals the Tumor-Suppressive and Immunoregulatory Roles of SEMA5B in Prostate Cancer","authors":"Zhiguo Fan,&nbsp;Yihaoyun Lou,&nbsp;Xuan Zhou,&nbsp;Guang Liu,&nbsp;Xiaomin Zhang,&nbsp;Yuanjie Tang,&nbsp;Zhen Zhu,&nbsp;Shancheng Ren,&nbsp;Yifan Chang","doi":"10.1002/biof.70133","DOIUrl":"10.1002/biof.70133","url":null,"abstract":"<p>SEMA5B plays an important role in the maintenance of neural development and is highly environment dependent in tumorigenesis. The roles of SEMA5B in prostate cancer remain underexplored. This study investigates SEMA5B's functions in prostate cancer, revealing its role as a tumor suppressor transcriptionally regulated by androgen receptor and uncovering novel biomarkers and potential immunotherapeutic mechanisms. We analyzed SEMA5B's expression in cancer and its spatial association with cells in the tumor microenvironment using single-cell transcriptome sequencing datasets and spatial transcriptome sequencing samples. Using bulk RNA-seq data, we analyzed the immune infiltration of SEMA5B in prostate cancer. The association of SEMA5B with androgen receptor signaling and with metabolic pathways was evaluated by transcriptome and enrichment analysis. The phenotypes, cell cycle, apoptosis, and mitochondrial metabolic function of prostate cancer cell lines were further evaluated. SEMA5B regulation by androgen receptor was examined by gene knockdown, androgen/enzalutamide treatment, and epigenomics. Finally, the effect of SEMA5B on prostate cancer in vivo was detected by tumor xenograft model. Pan-cancer single-cell analysis revealed that SEMA5B's expression showed significant tumor type specificity and spatially correlated with immune cell infiltration. SEMA5B is associated with abundant lymphocyte and immune-inflammatory microenvironment in prostate cancer. SEMA5B overexpression inhibited tumor cell proliferation, migration, and invasion. Moreover, high SEMA5B is associated with oxidative phosphorylation and low glycolytic profile. SEMA5B expression is positively correlated with androgen receptor. Androgen receptor inhibition and androgen stimulation affected the expression of SEMA5B. ChIP confirmed the binding of androgen receptor to the SEMA5B promoter. Finally, SEMA5B was verified to induce cell cycle arrest and apoptosis and reduce tumor growth. SEMA5B inhibits tumor malignant phenotype and is associated with immune-inflammatory tumor microenvironment. SEMA5B can regulate mitochondrial oxidative metabolism and induce cell cycle arrest and cell apoptosis, inhibiting the growth of prostate cancer.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpinia zerumbet-Derived Extracellular Vesicles Protect Against UVB-Induced Photoaging by Enhancing Mitochondrial Bioenergetics and Skin Barrier Function","authors":"Mo-Rong Xu,&nbsp;Hui-Chun Wang,&nbsp;Meng-Shiou Lee,&nbsp;Sheng-Yang Wang","doi":"10.1002/biof.70134","DOIUrl":"10.1002/biof.70134","url":null,"abstract":"<p>Ultraviolet B (UVB) radiation is a major cause of skin photoaging by oxidative stress, mitochondrial dysfunction, and barrier disruption. Plant-derived extracellular vesicles (PDEVs) have emerged as promising bioactive nanocarriers, but their roles in mitochondrial regulation and skin barrier homeostasis remain unclear. This study aimed to investigate the protective effects of extracellular vesicles derived from <i>Alpinia zerumbet</i> leaves (AZEVs) against UVB-induced photoaging in HaCaT keratinocytes. The results indicated that AZEVs exhibited typical extracellular vesicle characteristics, with an average size of 150 nm and a negative surface charge. Functionally, AZEVs significantly enhanced cell viability in UVB-exposed HaCaT cells, reduced ROS accumulation, and restored mitochondrial membrane potential and ATP production. Moreover, AZEVs upregulated mitochondrial biogenesis-related signaling pathway proteins (SIRT1, PGC-1<i>α</i>, Nrf2, and <i>p</i>-AMPK/AMPK) and TJ protein expression (ZO-1, occludin, and claudin-3), preserving barrier integrity and promoting wound healing. In addition, AZEVs are enriched in conserved miRNAs (miR166, miR159, and miR156) and a novel miRNA (novel_1), with predicted targets involved in redox regulation and energy metabolism. In summary, AZEVs protect keratinocytes against UVB-induced damage by enhancing mitochondrial function, reducing oxidative stress, and preserving skin barrier integrity. These findings highlight AZEVs as a promising natural nanoplatform for anti-photoaging and skin repair applications.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dauriporphine Inhibits the Proliferation, Migration, Angiogenesis, and Glycolysis in Lung Cancer Cells by Repressing PGK1 Expression via CEBPA","authors":"Pengxiao Hou,&nbsp;Zhizhong Liang,&nbsp;Qian Wu","doi":"10.1002/biof.70125","DOIUrl":"10.1002/biof.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>Many anti-cancer agents with therapeutic potential have been discovered in traditional Chinese medicine. Dauriporphine is an alkaloid extracted from <i>Menispermum dauricum DC.</i>, demonstrating anti-cancer properties. However, the precise role of dauriporphine in the treatment of lung cancer and its underlying biological mechanism remains unclear. Dauriporphine addition resulted in reduced proliferation, migration, angiogenesis, and glycolysis in A549 and H1299 cells. Phosphoglycerate kinase 1 (PGK1) was identified as the candidate gene involved in glycolysis and dauriporphine after prediction using public datasets. Dauriporphine administration decreased PGK1 expression, whereas PGK1 overexpression markedly abolished the suppressive effects of dauriporphine. The CCAAT/enhancer binding protein A (CEBPA) was predicted to be the transcription factor of PGK1 using the online QIAGEN. The binding between CEBPA and PGK1 promoter was predicted and verified using Jaspar algorithm and Human TFDB, as well as chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, and cellular thermal shift assay (CETSA). CEBPA silencing could repress tumor cell malignant behaviors, which could be partially restored by PGK1 overexpression. Moreover, the upregulation of CEBPA diminished the anti-tumor efficacy of dauriporphine. Furthermore, dauriporphine treatment suppressed tumor growth by regulating the CEBPA/PGK1 pathway in nude mice. Overall, the study demonstrated that dauriporphine inhibited proliferation, migration, angiogenesis, and glycolysis in lung cancer cells via the CEBPA/PGK1 pathway, providing a potentially effective therapeutic strategy for lung cancer.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Tumor Immune Ecosystem in Glioblastoma: Challenges and Innovations in Immunotherapy","authors":"Cheng Cheng,&nbsp;Yijue Wang,&nbsp;Yiru Wen,&nbsp;Yaqiang Bai,&nbsp;Yanni Xia,&nbsp;Yue Feng,&nbsp;Zeping Chen","doi":"10.1002/biof.70132","DOIUrl":"https://doi.org/10.1002/biof.70132","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma (GBM) is the most aggressive primary brain tumor, marked by poor prognosis and resistance to conventional therapies. A critical barrier to effective treatment lies in its highly immunosuppressive and heterogeneous tumor microenvironment (TME), which orchestrates immune evasion and therapeutic failure. Tumor-associated macrophages (TAMs), particularly those with an M2-like phenotype, sustain GBM proliferation, angiogenesis, and stem-like cell maintenance. Dysfunctional T lymphocytes—especially the accumulation of regulatory T cells—further attenuate anti-tumor immunity. Natural killer (NK) cells, dendritic cells, neutrophils, and myeloid-derived suppressor cells (MDSCs) also contribute to immune suppression through distinct yet interconnected mechanisms. Despite the success of immunotherapies in other malignancies, immune checkpoint inhibitors, CAR-T cells, and tumor vaccines have yielded limited efficacy in GBM, hindered by low neoantigen burden, antigenic heterogeneity, and poor immune infiltration. Overcoming these challenges requires a systems-level understanding of the immunoregulatory circuits within the GBM TME and the development of combination immunotherapies guided by predictive biomarkers. This review systematically delineates the roles of immune components in GBM immunopathology and outlines the emerging therapeutic strategies.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148357960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An AI-Driven Multi-Omics Framework Identifies CASP8 as a Clinically Actionable Pyroptosis Biomarker in Bladder Cancer","authors":"Zhigui Chen,&nbsp;ShouQiang Wang,&nbsp;Zhou Sun,&nbsp;Hengyi Liao,&nbsp;Yue Longji,&nbsp;Qiang Zhang,&nbsp;Jie Wang","doi":"10.1002/biof.70130","DOIUrl":"10.1002/biof.70130","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite rapid advances in multi-omics technologies, translating candidate biomarkers into clinical practice for bladder cancer remains challenging due to the difficulty of linking complex genomic instability to interpretable biological processes. To address this, we developed an AI-driven multi-omics discovery framework integrating single-cell RNA sequencing, multi-cohort transcriptomics, and machine learning–based genomic inference. By analyzing chromosomal aneuploidy and copy number variations at single-cell resolution, we identified malignant cell populations and constructed a consensus pyroptosis scoring system, followed by machine learning–assisted biomarker screening and experimental validation. Our results reveal that while global pyroptosis activity is elevated in the bladder cancer microenvironment, malignant cells with high genomic instability exhibit significant pyroptosis suppression. Through this pipeline, CASP8 was identified as a key clinically relevant biomarker; its low expression correlates strongly with increased tumor mutation burden, frequent driver gene alterations (including TP53 and RB1), and poor survival outcomes. Functional assays further confirmed that CASP8 loss promotes malignant phenotypes and alters cell death programs. Ultimately, this study establishes a next-generation framework for biomarker translation, highlighting CASP8 as a clinically actionable link between genomic instability and pyroptosis dysregulation, and demonstrating the power of AI-integrated strategies in accelerating bladder cancer research from bench to bedside.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 4","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelet-Related Gene Signature Predicts Prognosis, Immune Landscape, and Drug Sensitivity in Acute Myeloid Leukemia","authors":"Yi Wu,&nbsp;Wanjia Chen,&nbsp;Siqi Gong,&nbsp;Jiajia Wang,&nbsp;Zhimin Zhai","doi":"10.1002/biof.70123","DOIUrl":"10.1002/biof.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) remains challenging to treat due to clinical heterogeneity and a lack of prognostic biomarkers. To address this, we developed a prognostic signature based on platelet-related genes (PRGs). By analyzing transcriptomic data from TCGA-LAML, GSE146173, and Beat AML 2.0 cohorts, we identified and validated an 11-gene signature (PSME2, PPIF, SYTL4, S100A4, CCND3, SMIM15, PARVB, STXBP5, KCNMB1, GABRE, SLC50A1) using LASSO-Cox regression. This model effectively stratified patients into high- and low-risk groups with distinct survival outcomes (<i>p</i> &lt; 0.001) and demonstrated high predictive accuracy (1-/3-/5-year AUC: 0.832/0.782/0.880). High-risk patients exhibited immunosuppressive features, including upregulated immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1LG2, PDCD1), prominent monocyte infiltration, and reduced dendritic`11 cell activity. Drug sensitivity analysis suggested gefitinib, zebularine, and simvastatin as potential therapies for high-risk AML (<i>p</i> &lt; 0.05). We further validated the signature's prognostic value using qPCR and clinical grouping. Notably, in vitro studies indicated that KCNMB1 facilitates AML progression. In conclusion, our robust PRG-based model elucidates the link between platelet biology, immune dysregulation, and therapeutic vulnerability in AML, offering clinical utility for risk stratification and treatment decisions.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol-Derived Dimers With Antimicrobial and Immune-Enhancing Activities","authors":"Peter Riber Johnsen,&nbsp;Cecilia Pinna,&nbsp;Luca Andersen,&nbsp;Maria Vestergaard Christensen,&nbsp;Andrea Pinto,&nbsp;Sabrina Dallavalle,&nbsp;Hanne Ingmer,&nbsp;Hanne Frøkiær","doi":"10.1002/biof.70128","DOIUrl":"10.1002/biof.70128","url":null,"abstract":"<p>In search for novel antibiotic candidates, polyphenols represent an unexploited source with a nearly inexhaustible number of promising compounds. In addition to the antimicrobial activity, some polyphenols modulate the immune response in a way that could enhance the clearance of invading pathogens. This study investigated four resveratrol-derived dimeric compounds, dehydro-δ-viniferin, (±)-<i>trans</i>-δ-viniferin, viniferifuran, and (±)-ε-viniferin, for their antimicrobial activity against methicillin-resistant <i>S. aureus.</i> In addition, their immunomodulating properties in bacterially challenged dendritic cells were assessed. We identified dehydro-δ-viniferin as exhibiting the most potent antimicrobial activity against methicillin-resistant <i>Staphylococcus aureus</i> with a minimal inhibitory concentration of 2 μg/mL and a minimal bactericidal concentration of 8 μg/mL, respectively. Furthermore, dehydro-δ-viniferin showed significant enhancement of the <i>S. aureus</i>-induced IL-12 production from bone marrow-derived dendritic cells, which could be ascribed to a decrease in the production of IL-10. Only if dehydro-δ-viniferin was administered to dendritic cells prior to bacterial stimulation, IL-12 production was increased; if added later, the increase in IL-12 was lost although the IL-10 production was reduced. This suggests that dehydro-δ-viniferin interferes with the signaling pathway leading to IL-10, which in turn influences the IL-12 production in a time dependent manner. Collectively, dehydro-δ-viniferin is a potent antimicrobial against methicillin-resistant <i>S. aureus</i> with enhancing effects on the bacterially induced IL-12 response in antigen-presenting cells. We therefore suggest dehydro-δ-viniferin as a promising antibiotic candidate against multidrug-resistant Gram-positive bacteria.</p>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysine Lactylation: Dynamic Regulation in the Tumor Microenvironment and Clinical Translational Prospects","authors":"Yimao Wu,&nbsp;Xiaoyan Chen,&nbsp;Zichang Chen,&nbsp;Ruowei Sun,&nbsp;Qian Zhang,&nbsp;Gokhan Zengin,&nbsp;Meng-Yao Li","doi":"10.1002/biof.70126","DOIUrl":"10.1002/biof.70126","url":null,"abstract":"<div>\u0000 \u0000 <p>This review systematically explores the dynamic regulatory roles of lysine lactylation (Kla) in the tumor microenvironment (TME) and its clinical translational potential. As an emerging post-translational modification, Kla modifies histones and non-histone proteins via lactate generated by the Warburg effect, thereby reshaping tumor metabolism and immune landscapes. Mechanistically, Kla orchestrates metabolic reprogramming and immunosuppression through key signaling pathways such as HIF-1α, mTOR, and NF-κB. Specifically, it promotes the activation of immunosuppressive cells while inhibiting cytotoxic CD8⁺ T cells and NK cells, fostering tumor immune escape. Preclinical studies demonstrate that targeting lactate metabolism or lactylation enzymes restores immune effector functions and enhances immune checkpoint therapy efficacy. However, challenges such as tumor heterogeneity, metabolic plasticity, and systemic toxicity remain. Future research should focus on Kla's crosstalk with other epigenetic modifications, spatiotemporal dynamics in TIME, and clinical translation to unlock its potential as a biomarker and precision oncology target.</p>\u0000 </div>","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":"52 3","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}