ArticleExperimental and therapeutic medicine2019
Macrophage transcriptome modification induced by hypoxia and lactate.
Article in Experimental and therapeutic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Analysis of risk factors of fungal superinfections in viral pneumonia patients: A systematic review and meta-analysis.Immunity, inflammation and disease · 2023Pooled it
- Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model.International journal of molecular sciences · 2026Article
- Macrophages as Drivers of Resistance to Dabrafenib Plus Trametinib Therapy in Anaplastic Thyroid Cancer.International journal of molecular sciences · 2026Article
- Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- The RASSF1C-HIF-1α axis drives macrophage lipid metabolism to promote pancreatic cancer.Cell death & disease · 2026Article
- The double-edged sword role of tumor-associated macrophages: preventing or causing resistance to immunotherapy.Journal of experimental & clinical cancer research : CR · 2026Review
- Review
- Immunometabolic reprogramming in sepsis: mechanisms, clinical endotypes, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Increasing the health span: unique role for exercise.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Review
- Reprogramming the tumor microenvironment to overcome immunotherapy resistance in pancreatic cancer.Frontiers in immunology · 2025Review
- Targeting the hypoxia signaling pathway with nanomedicine to reverse immunotherapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Metabolic Reprogramming and Its Regulatory Mechanism in Sepsis-Mediated Inflammation.Journal of inflammation research · 2023Review
- Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy.Frontiers in immunology · 2023Review
- The Interface of Tumour-Associated Macrophages with Dying Cancer Cells in Immuno-Oncology.Cells · 2022Review
- The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies.Molecular cancer · 2022Review
- Cardiovascular Dysfunction in COVID-19: Association Between Endothelial Cell Injury and Lactate.Frontiers in immunology · 2022Review
- Developing a Diagnostic Model to Predict the Risk of Asthma Based on Ten Macrophage-Related Gene Signatures.BioMed research international · 2022Article
- Macrophages play a role in inflammatory transformation of colorectal cancer.World journal of gastrointestinal oncology · 2021Review
- Reshaping the Immune Microenvironment by Oncolytic Herpes Simplex Virus in Murine Pancreatic Ductal Adenocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer.Cell communication and signaling : CCS · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-depth bioinformatics analysis of previously published transcriptome data of macrophages was performed. A total of 6, 101 and 764 upregulated genes were identified in the lactate, hypoxia and hypoxia-lactate groups, respectively, whereas 4, 41 and 588 genes were downregulated in the same respective groups. Furthermore, differentially expressed genes (DEGs) of the hypoxia and hypoxia-lactate groups were significantly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway and the Hedgehog pathway. Upregulation of the mTOR and Hedgehog pathways in the hypoxia-lactate group was identified by gene set enrichment analysis. Furthermore, a set of HIF-1 pathway-associated genes was identified to be positively correlated with hypoxia using weighted gene co-expression network analysis. Lactate was indicated to inhibit the cell cycle in a hypoxia-independent manner. The DEGs of the hypoxia and hypoxia-lactate groups, including C-C motif chemokine receptor type 1 and 5, were enriched in the cytokine-cytokine receptor interaction pathway. In conclusion, under normoxic conditions, lactate exerted a weak effect on macrophages, while the combination of lactate and hypoxia markedly promoted the M2-polarization of macrophages via the HIF-1, Hedgehog and mTOR pathways. Lactate and hypoxia may also contribute to the formation of the spatial structure of tumor niches by inhibiting the proliferation of resident macrophages and by regulating the recruitment of peripheral macrophages.
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