ReviewFrontiers in immunology2024
From metabolic byproduct to immune modulator: the role of lactate in tumor immune escape.
Review in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Lactate as a Signaling Molecule in the Tumor Microenvironment: Implications for Cancer Progression.Biochemical genetics · 2026Review
- Metabolic reprogramming via LDHB confers resistance to lactate-induced dysfunction and enhanced antitumor activity in hiPSC-Derived NK cells.Stem cell reports · 2026Article
- Metabolic Reprogramming and Neurotransmitter Signaling Co-Option in the Glioma Immune Microenvironment: Dual-Axis Regulation of Immunosuppression.Biomolecules · 2026Review
- Pretreatment Lactate Dehydrogenase-to-Albumin Ratio and Clinical Outcomes in Extensive-Stage Small Cell Lung Cancer: A Multicenter Real-World Study.Journal of clinical medicine · 2026Article
- The RASSF1C-HIF-1α axis drives macrophage lipid metabolism to promote pancreatic cancer.Cell death & disease · 2026Article
- STC2 promotes colorectal cancer progression via c-Myc-mediated glycolysis and the PI3K/AKT/mTOR pathway.Discover oncology · 2026Article
- Article
- The enigmatic role of tumor dormancy cells in gynecologic cancers.Frontiers in immunology · 2026Review
- N4-acetylcytidine modification bridges metabolic reprogramming and immune evasion in cancer: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Myokine-mediated mechanisms of immune checkpoint inhibitors-associated colorectal injury and repair in rectal cancer.Frontiers in immunology · 2026Review
- Metabolic reprogramming and immune evasion interaction in the tumor microenvironment promote tumor progression.Frontiers in oncology · 2026Review
- The multifaceted functions of lactate and its translational potentials in cancer.Frontiers in pharmacology · 2026Review
- Metabolic reprogramming in ulcerative colitis: integrating dietary drivers, pathogenesis, and therapeutic advances.Frontiers in immunology · 2026Review
- Metabolite-driven dysfunction of intratumoral tertiary lymphoid structures: single-cell and spatial omics perspectives on cancer immune escape.Frontiers in immunology · 2026Review
- Targeting Lung Cancer Metabolism: Therapeutic Opportunities and Challenges.Advances in experimental medicine and biology · 2026Review
- Analyses of the Coexpression of Lactate Metabolism- and Ferroptosis-Related Genes in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Identification of lactylation and its hub genes in contributing immune activation and renal allograft fibrosis by integrative bioinformatics and machine learning.Frontiers in immunology · 2026Article
- Tumor lactate metabolism shapes immune suppression and therapeutic resistance revealed by integrative multi-omics and digital pathology.Frontiers in immunology · 2026Article
- Aerobic glycolysis-driven lactate accumulation and acidic tumor microenvironment in hepatocellular carcinoma: a vicious cycle promoting tumor progression.Frontiers in pharmacology · 2026Review
- Succinylation in cancer immunotherapy: mechanisms, biomarkers, and therapeutic implications.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactic acid, a key metabolic byproduct within the tumor microenvironment, has garnered significant attention for its role in immune evasion mechanisms. Tumor cells produce and release large amounts of lactic acid into the tumor microenvironment through aberrant glycolysis via the Warburg effect, leading to a drop in pH. Elevated lactic acid levels profoundly suppress proliferation capacity, cytotoxic functions, and migratory abilities of immune effector cells such as macrophages and natural killer cells at the tumor site. Moreover, lactic acid can modulate the expression of surface molecules on immune cells, interfering with their recognition and attack of tumor cells, and it regulates signaling pathways that promote the expansion and enhanced function of immunosuppressive cells like regulatory T cells, thereby fostering immune tolerance within the tumor microenvironment. Current research is actively exploring strategies targeting lactic acid metabolism to ameliorate tumor immune evasion. Key approaches under investigation include inhibiting the activity of critical enzymes in lactic acid production to reduce its synthesis or blocking lactate transporters to alter intracellular and extracellular lactate distribution. These methods hold promise when combined with existing immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapies to enhance the immune system's ability to eliminate tumor cells. This could pave the way for novel combinatorial treatment strategies in clinical cancer therapy, effectively overcoming tumor immune evasion phenomena, and ultimately improving overall treatment efficacy.
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