ArticleNature cell biology2026
Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.
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Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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22citing papers in PubMed
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22 citing papers in PubMed.
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cancer-derived lactic acid as a potential upstream contributor to tumor hypoxia.Communications biology · 2026Review
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Immunotherapy for Glioma: A compartmental framework for resistance and rational combination design.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Review
- Review
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- Review
- Cell-specific isotope labeling identifiesbioRxiv : the preprint server for biology · 2026Article
- Lactate metabolism-related interaction perturbation network enables robust stratification of hepatocellular carcinoma.Discover oncology · 2026Article
- Integrated Pan-Cancer, Single-Cell, and Spatial Transcriptomic Analyses Identify ZDHHC12 as a Biomarker Associated with Macrophage Infiltration and the Immune Landscape in Glioma.Journal of Cancer · 2026Article
- Editorial: Research on nanomaterials in tumor diagnosis and therapy, volume II.Frontiers in bioengineering and biotechnology · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- Glioma-intrinsic SLC1A3 hijacks the vascular niche to establish an immunosuppressive microenvironment.Frontiers in immunology · 2026Article
- Post-translational protein lactylation modification in lung cancer: an emerging targeted therapeutic strategy.Frontiers in immunology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
30 authors.
Daqi Li *National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0002-7448-7435
Gaoyuan Cui *National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Kailin Yang *Department of Radiation Oncology, Holden Comprehensive Cancer Center, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
Chenfei Lu *National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Yuhan Jiang *National Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Le Zhang *Analysis Center, Nanjing Medical University, Nanjing, China.
Qiulian WuLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Deobrat DixitDepartment of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
Zhe ZhuDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5385-948X
Ryan C GimpleDepartment of Medicine, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-7189-3243
Danling GuNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Jiancheng GaoNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Qiankun LinNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Hang YuNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Zhumei ShiDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Yun ChenInstitute for Brain Tumours, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0002-4118-362X
Qianghu WangInstitute for Brain Tumours, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0002-3488-1059
Guangfu JinInstitute for Brain Tumours, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Fan LinNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Junfei ShaoThe Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
Qigang ZhouDepartment of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Chong LiuDepartment of Neurosurgery of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Chaojun LiInstitute for Brain Tumours, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.ORCID http://orcid.org/0000-0001-9474-7321
Yongping YouDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Nu ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangdong Translational Medicine Innovation Platform, Guangzhou, China.ORCID http://orcid.org/0000-0002-2817-7065
Junxia ZhangDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. zjx232@njmu.edu.cn.ORCID http://orcid.org/0000-0003-1622-8045
Xu QianInstitute for Brain Tumours, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. xqianmedres@njmu.edu.cn.ORCID http://orcid.org/0000-0003-1533-8568
Qian ZhangNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. zhangqian01@njmu.edu.cn.ORCID http://orcid.org/0000-0002-6889-7112
Jeremy N RichLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. drjeremyrich@gmail.com.ORCID http://orcid.org/0000-0001-7845-5302
Xiuxing WangNational Health Commission Key Laboratory of Antibody Techniques, Department of Cell Biology, Jiangsu Provincial Key Laboratory of Human Functional Genomics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. drxiuxingwang@163.com.ORCID http://orcid.org/0000-0001-7115-729X
Funding
National Natural Science Foundation of China (National Science Foundation of China) 82525047National Natural Science Foundation of China (National Science Foundation of China) 82573312
Abstract
Glioblastoma (GBM) is a malignancy with a complex tumour microenvironment (TME) dominated by GBM stem cells (GSCs) and infiltrated by tumour-associated macrophages (TAMs) and exhibits aberrant metabolic pathways. Lactate is a critical glycolytic metabolite that promotes tumour progression; however, the mechanisms of lactate transport and lactylation in the TME of GBM remain elusive. Here we show that lactate is transported from TAMs to GSCs via MCT4-MCT1. TAMs provide lactate to GSCs, promoting GSC proliferation and inducing lactylation of the non-homologous end joining protein KU70 at lysine 317 (K317), which inhibits cGAS-STING signalling and remodels the immunosuppressive TME. Inhibition of lactate transport or targeting the lactylation of KU70, in combination with the immune checkpoint blockade, demonstrates additive therapeutic benefits in immunocompetent xenograft models. This study unveils TAM-derived lactate and lactylation as critical regulators in GSCs to enforce an immunosuppressive microenvironment, opening avenues for developing combinatorial therapy for GBM.
Indexed as
5'-NucleotidaseBrain NeoplasmsGlioblastomaLactic AcidMacrophagesMembrane ProteinsNucleotidyltransferasesTumor-Associated MacrophagesAnimalsCell Line, TumorCell ProliferationCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseFemaleHumansImmune Checkpoint InhibitorsMice5'-NucleotidasecGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseImmune Checkpoint InhibitorsLactic AcidMembrane ProteinsMonocarboxylic Acid TransportersNucleotidyltransferasesSTING1 protein, humanSTING ProteinSymporters
Identifiers
PMID
41495200What OpenQuestion holds
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.