Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy DOI Creative Commons
Md. Ataur Rahman,

Mahesh Kumar Yadab,

Meser M. Ali

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1924 - 1924

Published: Nov. 20, 2024

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function contributes failure. However, acidic conditions TME disrupt interaction between cancer cells, driving tumor-infiltrating T cells NK into an inactivated, anergic state. Simultaneously, promotes recruitment activation of immunosuppressive such as myeloid-derived suppressor regulatory (Tregs). Notably, acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor thus acts "protective shield," neutralizing anti-tumor responses transforming pro-tumor allies. Therefore, targeting lactate metabolism has emerged promising strategy overcome this barrier, with approaches including buffer agents neutralize pH inhibitors block production or transport, thereby restoring efficacy TME. Recent discoveries have identified genes involved (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims elucidate molecular mechanisms acidification develop treatments modulate levels enhance outcomes. Additionally, future studies are crucial validate safety pHe-targeted therapies patients. Thus, review explores regulation pHe its potential role improving immunotherapy.

Language: Английский

Role of Lactate in Inflammatory Processes: Friend or Foe DOI Creative Commons

Carolina Manosalva,

John Quiroga,

Alejandra I. Hidalgo

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 14, 2022

During an inflammatory process, shift in the cellular metabolism associated with increase extracellular acidification are well-known features. This pH drop inflamed tissue is largely attributed to presence of lactate by glycolysis. In recent years, evidence has accumulated describing role processes; however, there differences as whether can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these advances on pleiotropic effects process. Taken together, suggests that could exert differential depending metabolic status, cell type which studied, and pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor transcription factor activation such NF-κB HIF-1, allow modulate signaling pathways control expression cytokines, chemokines, adhesion molecules, several enzymes immune response metabolism. Altogether, this would explain its varied processes beyond waste product

Language: Английский

Citations

132
The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism DOI Open Access

Lingyu Tian,

Daniel J. Smit, Manfred Jücker

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2652 - 2652

Published: Jan. 31, 2023

Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition

Language: Английский

Citations

129
Unraveling tumor microenvironment of small-cell lung cancer: Implications for immunotherapy DOI
Tian Li,

Tianyun Qiao

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 117 - 125

Published: Sept. 29, 2022

Language: Английский

Citations

90
The role of lactate in cardiovascular diseases DOI Creative Commons
Jun Ouyang, Hui Wang, Jiangnan Huang

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 3, 2023

Abstract Cardiovascular diseases pose a major threat worldwide. Common cardiovascular include acute myocardial infarction (AMI), heart failure, atrial fibrillation (AF) and atherosclerosis. Glycolysis process often has changed during these diseases. Lactate, the end-product of glycolysis, been overlooked in past but gradually identified to play biological functions recent years. Similarly, role lactate disease is being recognized. Targeting production, regulating transport, modulating circulating levels may serve as potential strategies for treatment future. The purpose this review integrate relevant clinical basic research on pathophysiological years clarify important guide further studies exploring other

Language: Английский

Citations

57
Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer DOI Creative Commons

Minru Liao,

Dahong Yao,

Lifeng Wu

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 953 - 1008

Published: Dec. 16, 2023

Cancer reprogramming is an important facilitator of cancer development and survival, with tumor cells exhibiting a preference for aerobic glycolysis beyond oxidative phosphorylation, even under sufficient oxygen supply condition. This metabolic alteration, known as the Warburg effect, serves significant indicator malignant transformation. The effect primarily impacts occurrence by influencing pathway in cells. Key enzymes involved this process include glucose transporters (GLUTs), HKs, PFKs, LDHs, PKM2. Moreover, expression transcriptional regulatory factors proteins, such FOXM1, p53, NF-

Language: Английский

Citations

53
Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities DOI Creative Commons

Yujing Qian,

Yujia Yin,

Xiaocui Zheng

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 7, 2024

Abstract Tumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription but also external signals from the tumor microenvironment (TME), inflammatory metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit spectrum of activities ranging pro-tumorigenic anti-tumorigenic, closely associated with progression clinical prognosis. This review implicates diversity phenotypes functions, how this heterogeneity been re-evaluated advent single-cell technologies, impact TME on TAMs. We current therapies targeting metabolism offer new insights for TAM-dependent anti-tumor immunotherapy focusing critical role different programs

Language: Английский

Citations

22
Monocytes and macrophages: Origin, homing, differentiation, and functionality during inflammation DOI Creative Commons
Shiba Prasad Dash, Saloni Gupta, Pranita P. Sarangi

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(8), P. e29686 - e29686

Published: April 1, 2024

Monocytes and macrophages are essential components of innate immune system have versatile roles in homeostasis immunity. These phenotypically distinguishable mononuclear phagocytes play distinct different stages, contributing to the pathophysiology various forms making them a potentially attractive therapeutic target inflammatory conditions. Several pieces evidence supported role cell surface receptors expressed on these cells their downstream signaling molecules initiating perpetuating response. In this review, we discuss current understanding monocyte macrophage biology inflammation, highlighting chemoattractants, inflammasomes, integrins function monocytes during events inflammation. This review also covers recent interventions targeting at cellular molecular levels.

Language: Английский

Citations

18
The lactate sensor GPR81 regulates glycolysis and tumor growth of breast cancer DOI Creative Commons

Shota Ishihara,

Kenji Hata, Katsutoshi Hirose

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: April 15, 2022

Metabolic reprogramming is a malignant phenotype of cancer. Cancer cells utilize glycolysis to fuel rapid proliferation even in the presence oxygen, and elevated coupled lactate fermentation cancer microenvironment. Although has been recognized as metabolic waste product, it become evident that functions not only an energy source but signaling molecule through receptor G-protein-coupled 81 (GPR81) under physiological conditions. However, pathological role GPR81 remains unclear. Here, we show regulates breast cell by metabolism. We found highly expressed lines normal epithelial cells. Knockdown decreased proliferation, tumor growth. Mechanistically, lactate-dependent ATP production were impaired GPR81-silenced RNA sequencing accompanied Gene Ontology enrichment analysis further demonstrated significant decrease genes associated with motility silencing suppressed migration invasion. Notably, histological examination showed strong expression clinical samples human Collectively, our findings suggest critical for malignancy may be potential novel therapeutic target carcinoma.

Language: Английский

Citations

53
Probiotic-Functionalized Silk Fibroin/Sodium Alginate Scaffolds with Endoplasmic Reticulum Stress-Relieving Properties for Promoted Scarless Wound Healing DOI
Zhaona Dou, Binbin Li, Lin Wu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(5), P. 6297 - 6311

Published: Jan. 26, 2023

Bioactive substances such as probiotics are becoming a research hotspot in the field of tissue regeneration due to their excellent regulatory functions. Here, we proposed load Lactobacillus casei onto bilayer silk fibroin/sodium alginate (SF/SA) scaffold endow with both antibacterial and regenerative properties. The performance was characterized systemically. L. casei-loaded scaffolds (L-SF/SA) bring lactic acid, which has wound healing In vitro, cell-free supernatant (CFS) inhibited transformation fibroblasts myofibroblasts relieved endoplasmic reticulum stress (ERS). vivo, L-SF/SA accelerated infected wounds SD rats. reduced bacterial load, induced M2 polarization macrophages, increased angiogenesis, regulated collagen ratio, alleviated ERS, thereby promoting scarless increasing hair follicle regeneration. Therefore, probiotic-functionalized fibroin/alginate showed potential healing.

Language: Английский

Citations

28
Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy DOI Creative Commons
Hongxia Tao,

Xuansheng Zhong,

Anqi Zeng

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 26, 2023

Lactate, traditionally regarded as a metabolic waste product at the terminal of glycolysis process, has recently been found to have multifaceted functional roles in metabolism and beyond. A reprogramming phenomenon commonly seen tumor cells, known "Warburg effect," sees high levels aerobic result an excessive production lactate. This lactate serves substrate that sustains not only survival cancer cells but also immune cells. However, it inhibits function tumor-associated macrophages (TAMs), group innate ubiquitously present solid tumors, thereby facilitating evasion malignant Characterized by their plasticity, TAMs are generally divided into pro-inflammatory M1 phenotype pro-tumour M2 phenotype. Through process 'education' lactate, tend adopt immunosuppressive collaborate with promote angiogenesis. Additionally, there is growing evidence linking epigenetic modifications, suggesting participation histone modification diverse cellular events within microenvironment (TME). In this review, we delve recent discoveries concerning particular focus on impact TAMs. We aim consolidate molecular mechanisms underlying lactate-induced TAM polarization angiogenesis explore lactate-mediated crosstalk between Finally, touch upon latest progress immunometabolic therapies drug delivery strategies targeting production, offering new perspectives for future therapeutic approaches.

Language: Английский

Citations

28