Biomarker Research最新文献

{"title":"ROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2.","authors":"Dan Li, Wenjie Zhang, Ruiheng Wang, Shufeng Xie, Yixin Wang, Wanxin Guo, Zixuan Huang, Chaoqun Lu, Liang Shan, Han Liu, Lifang Ma, Xumin Hou, Zhenshu Xu, Jiayi Wang","doi":"10.1186/s40364-025-00730-0","DOIUrl":"10.1186/s40364-025-00730-0","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer, particularly non-small cell lung cancer (NSCLC), has high recurrence rates and remains a leading cause of cancer-related death, despite recent advances in its treatment. Emerging therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown promise but face significant challenges in targeting solid tumors. This study investigated the potential of combining receptor tyrosine kinase-like orphan receptor 1 (ROR1)-targeting CAR-T cells with ferroptosis inducers to promote ferroptosis of tumor cells and enhance anti-tumor efficacy.</p><p><strong>Methods: </strong>RNA-seq data and immunofluorescence analysis of relapsed NSCLC patient samples were used to explore ROR1 expression. In addition, ROR1-targeting CAR-T cells were developed to assess cytotoxic activity against ROR1⁺ tumor cells, and the effect of cytokine stimulation on their efficacy was evaluated. Lipidomics, immunofluorescent histochemistry, and western blotting were used to explore the observed effects. Ferroptosis indicators, including levels of reactive oxygen species, were used to detect the combined effect of CAR-T cells and ferroptosis-inducing drugs. Finally, tumor-bearing mice were used to validate the in vivo efficacy of the combination therapy strategy.</p><p><strong>Results: </strong>Tumor cells treated with ferroptosis inducers showed increased sensitivity to Interferon gamma (IFN-γ) secreted by ROR1 CAR-T cells. Furthermore, ROR1 CAR-T cells enhanced the production of phosphatidylcholine with diacyl-polyunsaturated fatty acid tails (PC-PUFA2) by working in tandem with IFN-γ. This enhancement promoted the expression of acyl-CoA synthetase long chain family member 4 (ACSL4), which in turn strengthened the overall anti-tumor response.</p><p><strong>Conclusions: </strong>Combining ROR1 CAR-T cells with ferroptosis inducers enhanced anti-tumor efficacy in NSCLC by promoting ferroptosis through increased lipid peroxidation.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"17"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, regional, and national burden of heart failure and its underlying causes, 1990-2021: results from the global burden of disease study 2021.","authors":"Jun Ran, Ping Zhou, Jinxi Wang, Xuemei Zhao, Yan Huang, Qiong Zhou, Mei Zhai, Yuhui Zhang","doi":"10.1186/s40364-025-00728-8","DOIUrl":"10.1186/s40364-025-00728-8","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) remains a significant public health challenge globally. This study aims to systematically analyze the global HF disease burden from 1990 to 2021 across temporal, spatial, and demographic dimensions to provide evidence for targeted prevention and control strategies.</p><p><strong>Methods: </strong>Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed the global HF burden through prevalent cases, years lived with disability (YLDs), and age-standardized rates per 100,000 population. Temporal trends were evaluated using estimated annual percentage change (EAPC) and joinpoint regression analysis. The relationship between the Socio-demographic Index (SDI) and disease burden was explored through Pearson correlation analysis, while attribution analysis identified the main causes of HF. When appropriate, analyses were stratified by 5 SDI regions, 21 GBD regions, 204 countries and territories, 20 age groups, and both sexes.</p><p><strong>Results: </strong>Global HF prevalence and YLDs burden showed substantial increases from 1990 to 2021, with age-standardized prevalence increasing from 641.14 to 676.68 per 100,000 population. Notably, high-SDI regions exhibited a declining burden since 2019, indicating a potential global turning point. High-income North America bears the heaviest burden while South Asia shows the fastest growth rate. The correlation between disease burden and SDI level was negligible. The disease burden in males consistently exceeded that in females, with prevalence and YLDs rates rising sharply after age 60. The main causes and their attributable proportions were: ischemic heart disease (34.53%), hypertensive heart disease (22.53%), other cardiomyopathies (7.61%), chronic obstructive pulmonary disease (6.51%), and congenital heart anomalies (5.69%), with their distribution patterns differing across age groups and regions.</p><p><strong>Conclusion: </strong>Global burden of HF increased significantly over recent decades, with a potential turning point in 2019 and marked regional disparities. It is essential to prioritize regions with heavy burdens or rapid growth rates, strengthen the management of major causes, and monitor HF burden trends in the post-COVID era.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"16"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030300","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":"Real-world use of tafasitamab preceding CD19-directed chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma.","authors":"Narendranath Epperla, Loretta J Nastoupil, Bruce Feinberg, John Galvin, Prathamesh Pathak, Theresa Amoloja, Danielle Gentile, Kim Saverno","doi":"10.1186/s40364-024-00706-6","DOIUrl":"10.1186/s40364-024-00706-6","url":null,"abstract":"<p><p>Potential CD19 antigen loss following CD19-directed therapy has raised concerns over sequential use of these therapies. Tafasitamab, a CD19-targeting immunotherapy, combined with lenalidomide, is approved for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) treatment in adults ineligible for autologous stem cell transplantation. This retrospective analysis examined characteristics and outcomes of adults with R/R DLBCL who received tafasitamab preceding CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy in a real-world setting. Nine patients received tafasitamab and lenalidomide immediately preceding CAR-T. Median (first quartile [Q1]-third quartile [Q3]) follow-up time since tafasitamab initiation was 26.1 (18.0-28.0) and after CAR-T was 9.3 (1.9-16.7) months. Of the 9 patients, 4 had complete response, 4 had partial response, and 1 had stable disease following tafasitamab; all discontinued tafasitamab due to disease progression. Median (Q1-Q3) tafasitamab therapy duration was 11.0 (8.1-14.1) months. Three patients had CD19 testing following tafasitamab discontinuation, and all tests were positive. Median (Q1-Q3) time from tafasitamab discontinuation to CD19 testing was 7 (6-9) days. Among the 9 patients, median (Q1-Q3) time from tafasitamab discontinuation to CAR-T administration was 3.2 (2.3-3.6) months. Four patients had complete response, 3 had partial response, and 1 had progressive disease as best response to CAR-T; 1 patient had data unavailable. This small real-world analysis demonstrated disease response to CAR-T therapy and detectable CD19 expression following tafasitamab treatment, adding to literature investigating treatment outcomes associated with sequential use of anti-CD19 therapies in patients with R/R DLBCL.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"18"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030313","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":"Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression.","authors":"Yicheng Zhu, Jiaoshun Chen, Chen Chen, Rong Tang, Jin Xu, Si Shi, Xianjun Yu","doi":"10.1186/s40364-025-00727-9","DOIUrl":"10.1186/s40364-025-00727-9","url":null,"abstract":"<p><p>The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising a diverse array of cellular and non-cellular components that precisely orchestrate pivotal tumor behaviors, including invasion, metastasis, and drug resistance. While unraveling the intricate interplay between the tumor microenvironment and tumor behaviors represents a tremendous challenge, recent research illuminates a crucial biological phenomenon known as cellular mechanotransduction. Within the microenvironment, mechanical cues like tensile stress, shear stress, and stiffness play a pivotal role by activating mechanosensitive effectors such as PIEZO proteins, integrins, and Yes-associated protein. This activation initiates cascades of intrinsic signaling pathways, effectively linking the physical properties of tissues to their physiological and pathophysiological processes like morphogenesis, regeneration, and immunity. This mechanistic insight offers a novel perspective on how the mechanical cues within the tumor microenvironment impact tumor behaviors. While the intricacies of the mechanical tumor microenvironment are yet to be fully elucidated, it exhibits distinct physical attributes from non-malignant tissues, including elevated solid stresses, interstitial hypertension, augmented matrix stiffness, and enhanced viscoelasticity. These traits exert notable influences on tumor progression and treatment responses, enriching our comprehension of the multifaceted nature of the microenvironment. Through this innovative review, we aim to provide a new lens to decipher the mechanical attributes within the tumor microenvironment from non-malignant contexts, broadening our knowledge on how these factors promote or inhibit tumor behaviors, and thus offering valuable insights to identify potential targets for anti-tumor strategies.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"11"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030294","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":"Neutrophil extracellular traps in tumor metabolism and microenvironment.","authors":"Zhanrui Liu, Yuanyao Dou, Conghua Lu, Rui Han, Yong He","doi":"10.1186/s40364-025-00731-z","DOIUrl":"10.1186/s40364-025-00731-z","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are intricate, web-like formations composed of DNA, histones, and antimicrobial proteins, released by neutrophils. These structures participate in a wide array of physiological and pathological activities, including immune rheumatic diseases and damage to target organs. Recently, the connection between NETs and cancer has garnered significant attention. Within the tumor microenvironment and metabolism, NETs exhibit multifaceted roles, such as promoting the proliferation and migration of tumor cells, influencing redox balance, triggering angiogenesis, and driving metabolic reprogramming. This review offers a comprehensive analysis of the link between NETs and tumor metabolism, emphasizing areas that remain underexplored. These include the interaction of NETs with tumor mitochondria, their effect on redox states within tumors, their involvement in metabolic reprogramming, and their contribution to angiogenesis in tumors. Such insights lay a theoretical foundation for a deeper understanding of the role of NETs in cancer development. Moreover, the review also delves into potential therapeutic strategies that target NETs and suggests future research directions, offering new perspectives on the treatment of cancer and other related diseases.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"12"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030302","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":"Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes.","authors":"Claudia Omarini, Virginia Catani, Ilenia Mastrolia, Angela Toss, Federico Banchelli, Chrystel Isca, Daniele Medici, Ornella Ponzoni, Marco Brucale, Francesco Valle, Maria Cristina Baschieri, Roberto D'Amico, Valentina Masciale, Chiara Chiavelli, Federica Caggia, Carlo Augusto Bortolotti, Federico Piacentini, Massimo Dominici","doi":"10.1186/s40364-025-00724-y","DOIUrl":"10.1186/s40364-025-00724-y","url":null,"abstract":"<p><p>Emerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. However, limited knowledge exists on the levels and clinical meaning of miR-21 in extracellular vesicles (EVs) of patients with breast cancer (BC). We assessed EV-derived miR-21 levels in one hundred women: 30 with early BC (EBC), 30 with metastatic BC on treatment progression (MBC), 30 cancer survivors on follow-up (FU) and 10 healthy donors (HD) as age- and body mass index (BMI)-matched controls. EVs isolated from serum samples were characterized using nanoparticle tracking analysis, scanning electron microscopy and atomic force microscopy to detect their concentration, size, morphology and mechanical properties. The levels of miR-21 in EVs was evaluated using real time PCR and compared between groups (EBC, MBC and FU vs. HD) by calculating the fold change and ΔΔCt statistic. EVs size and concentration did not differ significantly among patient groups. In the EBC group, the clinical stage at diagnosis and tumor subtype did not influence miR-21 levels. The levels of miR-21 were higher in the MBC group than in the HD group (p = 0.029), mainly in those who were human epidermal growth factor receptor 2 (HER2)+ (p = 0.0005) and hormone receptor-positive (p = 0.036). In particular, in the HER2 + subgroup, the miR-21 levels were significantly higher in those with active BC (both EBC and MBC) than in HDs (p = 0.002). Our findings suggest that miR-21 may be a promising biomarker for diagnosis and tumor activity, mainly in HER2 + BC.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"14"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030298","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: A pair of promising immune checkpoints PSGL-1 and VISTA from immunotolerance to immunotherapy.","authors":"Manqing Peng, Xiaofang Lu, Junshuang Guo, Xiangli Yin, Jing Zhang, Xin Li, Yizhou Zou","doi":"10.1186/s40364-024-00709-3","DOIUrl":"10.1186/s40364-024-00709-3","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"19"},"PeriodicalIF":9.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030269","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 prognostic value of systemic immune-inflammation index in patients with unresectable hepatocellular carcinoma treated with immune-based therapy.","authors":"Tian He, Bin Xu, Lu-Na Wang, Zi-Yi Wang, Huan-Chen Shi, Cheng-Jie Zhong, Xiao-Dong Zhu, Ying-Hao Shen, Jian Zhou, Jia Fan, Hui-Chuan Sun, Bo Hu, Cheng Huang","doi":"10.1186/s40364-024-00722-6","DOIUrl":"10.1186/s40364-024-00722-6","url":null,"abstract":"<p><strong>Background: </strong>Predicting the efficacy of immune-based therapy in patients with unresectable hepatocellular carcinoma (HCC) remains a clinical challenge. This study aims to evaluate the prognostic value of the systemic immune-inflammation index (SII) in forecasting treatment response and survival outcomes for HCC patients undergoing immune-based therapy.</p><p><strong>Methods: </strong>We analyzed a cohort of 268 HCC patients treated with immune-based therapy from January 2019 to March 2023. A training cohort of 93 patients received atezolizumab plus bevacizumab (T + A), while a validation cohort of 175 patients underwent treatment with tyrosine kinase inhibitors (TKIs) combined with anti-PD-(L)1 therapy. The SII cutoff value, determined using X-tile analysis based on overall survival (OS) in the training cohort, divided patients into high (> 752*10⁹) and low (≤ 752*10⁹) SII groups. Prognostic factors were identified through univariate and multivariate logistic and Cox regression analyses, and survival outcomes were assessed using Kaplan-Meier methods. The predictive accuracy of SII was evaluated using receiver operating characteristic (ROC) curves.</p><p><strong>Results: </strong>An optimal SII cutoff of 752*10⁹ stratified patients into high and low SII groups. Univariate and multivariate logistic regression indicated that SII was a significant predictor of the objective response rate (ORR), which was markedly different between the low and high SII subgroups (34.72% vs. 9.52%, P = 0.019). This finding was consistent in the validation cohort (34.09% vs. 16.28%, P = 0.026). SII also demonstrated prognostic value in Cox regression and Kaplan-Meier analyses. ROC curves confirmed that SII had superior predictive accuracy compared to common clinical indicators, with predictive relevance even in AFP-negative patients. Furthermore, a lower SII was associated with a higher T cell ratio and an increased number of CD8⁺ T cells and Granzyme B⁺ CD8⁺ T cells in peripheral blood.</p><p><strong>Conclusion: </strong>SII is a promising predictor of both therapeutic efficacy and prognosis in HCC patients undergoing immune-based treatments. Its application may enhance clinical decision-making, thereby improving patient outcomes from immune-based therapy.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"10"},"PeriodicalIF":9.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980855","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: Global burden of breast cancer and attributable risk factors in 204 countries and territories, from 1990 to 2021: results from the global burden of Disease Study 2021.","authors":"Rui Sha, Xiang-Meng Kong, Xin-Yu Li, Ya-Bing Wang","doi":"10.1186/s40364-025-00729-7","DOIUrl":"10.1186/s40364-025-00729-7","url":null,"abstract":"","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"9"},"PeriodicalIF":9.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973279","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":"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/s40364-024-00719-1","DOIUrl":"10.1186/s40364-024-00719-1","url":null,"abstract":"<p><strong>Background: </strong>Although immunotherapy has achieved great progress in advanced triple-negative breast cancer (TNBC), there are still numerous patients who do not benefit from immunotherapy. Therefore, identification of the key molecule that induces immune escape and clarification of its specific mechanism in TNBC are urgently needed.</p><p><strong>Methods: </strong>In this research, single cell sequencing and bulk sequencing were conducted for biomarker screening. Immunohistochemistry, multiplex immunofluorescence, and orthotopic TNBC tumor model were applied in identifying the key molecule driving immune escape. At the mechanical level, RNA sequencing, in vitro co-culturing system, flow cytometry, Western blotting, ELISA, and real-time qPCR were carried out.</p><p><strong>Results: </strong>Mortality factor 4 like 2 (MORF4L2) expression is significantly up-regulated among patients who developed anti-PD1 resistance. MORF4L2 enhances anti-PD1 resistance by inducing the chemotaxis of macrophage infiltration and promoting their polarization towards the alternative activation phenotype (M2), thus creating an immunosuppressive microenvironment. Mechanistically, MORF4L2 actes as part of NuA4 histone acetyltransferase (HAT) complex, contributes to to histone 4 lysine 12 acetylation (H4K12Ac) and activates the downstream transcription of macrophage colony-stimulating factor (CSF1). CSF1 is secreted by tumor cells and binds to the macrophage-surface CSF1 receptor (CSF1R), which chemotactically converted and polarized macrophages to the M2 phenotype. Furthermore, we revealed that grainyhead like transcription factor 2 (GRHL2) could promote MORF4L2 transcription by binding to the MORF4L2 enhancer region. Notably, BLZ549, an inhibitor of CSF1R, restored the anti-PD1 sensitivity by blocking the GRHL2/MORF4L2/H4K12Ac/CSF1 axis.</p><p><strong>Conclusions: </strong>GRHL2/MORF4L2/H4K12Ac/CSF1 axis plays an important role in anti-PD1 resistance. CSF1R inhibitors can reverse GRHL2/MORF4L2-mediated anti-PD1 resistance.</p>","PeriodicalId":54225,"journal":{"name":"Biomarker Research","volume":"13 1","pages":"6"},"PeriodicalIF":9.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11715975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958521","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}