Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: 408, P. 111418 - 111418
Published: Feb. 1, 2025
Language: Английский
Cancer Cell, Journal Year: 2021, Volume and Issue: 40(1), P. 70 - 87.e15
Published: Dec. 30, 2021
Language: Английский
Citations
232
Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12
Published: Oct. 18, 2021
Lactate and the associated H + ions are still introduced in many biochemistry general biology textbooks courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, role of lactate fuel source has been well-appreciated field physiology, feedback regulator distinct signaling molecule is beginning to gain traction immunology. We now know that while generally immunosuppressive negative regulators, there cell, receptor, mediator, microenvironment-specific effects augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, neutrophil functions. Moreover, we uncover how utilize different transporters cascades various immune cell types. These immunomodulatory may have substantial impact cancer, sepsis, autoimmunity, wound healing, other conditions with elevated levels. In this article, summarize known on cells hypothesize potential explanations for divergent inflammatory vs. anti-inflammatory effects.
Language: Английский
Citations
114
Hepatology, Journal Year: 2022, Volume and Issue: 77(1), P. 109 - 123
Published: Jan. 19, 2022
Background and Aims: Monocarboxylate transporter (MCT) 4 is a high‐affinity lactate that primarily involved in the maintenance of intracellular pH homeostasis highly expressed different tumors. However, role MCT4 modulating immune responses against HCC remains unknown. Approach Results: In this study, we demonstrated was overexpressed HCC, which associated with poor prognosis patients. Genetic or pharmacological inhibition using VB124 (a potent inhibitor) suppressed tumor growth immunocompetent mice model by enhancing CD8 + T cell infiltration cytotoxicity. Such improved immunotherapy response targeting due to combined consequences characterized alleviated acidification microenvironment elevated chemokine (C‐X‐C motif) ligand (CXCL) 9/CXCL10 secretion induced reactive oxygen species/NF‐κB signaling pathway. Combining therapeutic benefit anti–programmed death 1 prolonged survival. Moreover, higher expression observed tissues from nonresponder patients receiving neoadjuvant therapy toripalimab. Conclusions: Our results revealed exportation has tumor‐intrinsic function generating an immunosuppressive environment proof concept tailoring immunotherapeutic approaches.
Language: Английский
Citations
77
Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 157, P. 113993 - 113993
Published: Nov. 12, 2022
Abnormal energy metabolism, as one of the important hallmarks cancer, was induced by multiple carcinogenic factors and tumor-specific microenvironments. It comprises aerobic glycolysis, de novo lipid biosynthesis, glutamine-dependent anaplerosis. Considering that metabolic reprogramming provides various nutrients for tumor survival development, it has been considered a potential target cancer therapy. Cannabinoids have shown to exhibit variety anticancer activities unclear mechanisms. This paper first reviews recent progress related signaling pathways (reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mitogen-activated kinases (MAPK), phosphoinositide 3-kinase (PI3K), hypoxia-inducible factor-1alpha (HIF-1α), p53) mediating metabolism (including glucose amino acid metabolism). Then we comprehensively explore latest discoveries possible mechanisms effects cannabinoids through regulation above-mentioned pathways, provide new targets insights prevention treatment.
Language: Английский
Citations
74
Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(8), P. 1208 - 1222
Published: July 13, 2023
Language: Английский
Citations
69
Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 90, P. 1 - 14
Published: Jan. 24, 2023
Language: Английский
Citations
63
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3142 - 3142
Published: March 8, 2024
The Warburg effect, characterized by the preferential conversion of glucose to lactate even in presence oxygen and functional mitochondria, is a prominent metabolic hallmark cancer cells has emerged as promising therapeutic target for therapy. Elevated levels acidic pH within tumor microenvironment (TME) resulting from glycolytic profoundly impact various cellular populations, including macrophage reprogramming impairment T-cell functionality. Altogether, effect been shown promote progression immunosuppression through multiple mechanisms. This review provides an overview current understanding its implications. We summarize recent pharmacological strategies aimed at targeting enzymes, highlighting challenges encountered achieving efficacy. Additionally, we examine utility early diagnostic tool. Finally, discuss multifaceted roles TME, emphasizing potential disrupt interactions between immune cells, thereby enhancing anti-tumor immunity.
Language: Английский
Citations
61
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Jan. 31, 2024
The liver is essential for metabolic homeostasis. onset of cancer often accompanied by dysregulated function, leading to rearrangements. Overwhelming evidence has illustrated that cellular metabolism can, in turn, promote anabolic growth and tumor propagation a hostile microenvironment. In addition supporting continuous survival, disrupted process also creates obstacles the anticancer immune response restrains durable clinical remission following immunotherapy. this review, we elucidate communication between cells their surrounding discuss how reprogramming impacts microenvironment efficacy We describe crucial role gut-liver axis remodeling crosstalk surveillance escape, highlighting novel therapeutic opportunities.
Language: Английский
Citations
45
Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114180 - 114180
Published: May 1, 2024
Macrophage activation is a hallmark of atherosclerosis, accompanied by switch in core metabolism from oxidative phosphorylation to glycolysis. The crosstalk between metabolic rewiring and histone modifications macrophages worthy further investigation. Here, we find that lactate efflux-associated monocarboxylate transporter 4 (MCT4)-mediated lactylation closely related atherosclerosis. Histone H3 lysine 18 dependent on MCT4 deficiency activated the transcription anti-inflammatory genes tricarboxylic acid cycle genes, resulting initiation local repair homeostasis. Strikingly, characteristically involved stage-specific process during M1 M2 transformation, whereas methylation acetylation are not. Gene manipulation protein hydrolysis-targeted chimerism technology used confirm favors ameliorating Therefore, our study shows macrophage deficiency, which links modifications, plays key role training become homeostasis phenotypes.
Language: Английский
Citations
24
Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)
Published: April 24, 2020
Abstract Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in efficacy are highly sensitive to stress, yet whether astrocyte bioenergetic control synapses contributes stress-impaired plasticity is unclear. Here we show mice that stress constrains shuttling glucose lactate through networks, creating a barrier for neuronal access an astrocytic reservoir hippocampus neocortex, compromising long-term potentiation. Impairing delivery substrates by reducing gap junction coupling with dominant negative connexin 43 or disrupting efflux was sufficient mimic effects on Furthermore, direct restoration supply alone rescued plasticity, which blocked inhibiting neural uptake. This gating metabolic networks indicates broader role bioenergetics determining how experience-dependent information controlled.
Language: Английский
Citations
132