The Role and Clinical Relevance of Glycolysis‐Associated Genes on Immune Infiltration in Hepatocellular Carcinoma DOI
Jing Li, Peng Su, Ting Li

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(8)

Published: June 25, 2024

Hepatocellular carcinoma (HCC) poses a significant challenge with dismal survival rates, necessitating deeper understanding of its molecular mechanisms and the development improved therapies. Metabolic reprogramming, particularly heightened glycolysis, plays crucial role in HCC progression. Glycolysis-associated genes (GAGs) emerge as key players pathogenesis, influencing tumor microenvironment immune responses. This study aims to investigate intricate interplay between GAGs landscape within HCC, offering valuable insights into potential prognostic markers therapeutic targets enhance treatment strategies patient outcomes. Through exploration GAGs, we have identified two distinct glycolytic subtypes patients, each exhibiting differences both prognosis. A risk model comprising five was formulated subsequently evaluated for their predictive accuracy. Our findings underscore diverse responses associated varying observed HCC. The hold promise indicators evaluating levels, predicting outcomes, guiding clinical decisions, context anticipating immunotherapy drugs.

Language: Английский

Glycolysis, the sweet appetite of the tumor microenvironment DOI Creative Commons

Zeinab Kooshan,

Lilibeth Cárdenas-Piedra,

Judith A. Clements

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 600, P. 217156 - 217156

Published: Aug. 8, 2024

Cancer cells display an altered metabolic phenotype, characterised by increased glycolysis and lactate production, even in the presence of sufficient oxygen - a phenomenon known as Warburg effect. This reprogramming is crucial adaptation that enables cancer to meet their elevated energy biosynthetic demands. Importantly, tumor microenvironment plays pivotal role shaping sustaining this shift cells. review explores intricate relationship between effect, highlighting how communication within niche regulates cell metabolism impacts progression therapeutic resistance. We discuss potential targeting effect promising strategy, with aim disrupting advantage enhancing our understanding complex interplay microenvironment.

Language: Английский

Citations

18
Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming DOI Creative Commons
Ting Yu, Zhaoyun Liu,

Qingxu Tao

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 589, P. 216824 - 216824

Published: March 23, 2024

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized clinical practice within the last decade. However, primary and secondary resistance to immunotherapy is common in patients with diverse types of cancer. It well-acknowledged that tumor cells can facilitate formation immunosuppressive microenvironments via metabolism reprogramming, lactic acid, metabolite glycolysis, a significant contributor. SLC16A3 (also named as MCT4) transporter mediating acid efflux. In this study, we investigated role glycolysis aimed improve effects Slc16a3 inhibition. Bioinformatical analysis revealed expression glycolysis-related genes correlated less CD8

Language: Английский

Citations

14
Triple Negative Breast Cancer: Molecular Subtype-Specific Immune Landscapes with Therapeutic Implications DOI Open Access
Antonia Syrnioti, Stamatios Petousis, Lisa A. Newman

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 2094 - 2094

Published: May 31, 2024

Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in tumor immune microenvironment (TIME) across different TNBC subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling bioinformatic analyses classify samples into subtypes, as well immunohistochemistry cell deconvolution methods characterize TIME. Results revealed significant heterogeneity composition among immunomodulatory (IM) subtype demonstrating robust infiltration, composed mainly of adaptive cells along an increased density CTLA-4+ PD-1+ TILs, high PD-L1 expression, upregulation FOXP3+ Tregs. A more immunosuppressive TIME a predominance innate lower levels tumor-infiltrating lymphocytes (TILs) was observed luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, cells, number M2 tumor-associated macrophages (TAMs), while BL M tumors displayed poor responses, indicating “immune-cold” phenotype. Differential activation signaling pathways, genomic diversity, metabolic reprogramming identified contributors heterogeneity. Understanding this interplay crucial for tailoring therapeutic strategies, especially regarding immunotherapy.

Language: Английский

Citations

13
Metabolic crossroads: unravelling immune cell dynamics in gastrointestinal cancer drug resistance DOI Open Access

C. Raman Suri,

Babita Pande,

Lakkakula Suhasini Sahithi

et al.

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Metabolic reprogramming within the tumor microenvironment (TME) plays a critical role in driving drug resistance gastrointestinal cancers (GI), particularly through pathways of fatty acid oxidation and glycolysis. Cancer cells often rewire their metabolism to sustain growth reshape TME, creating conditions such as nutrient depletion, hypoxia, acidity that impair antitumor immune responses. Immune TME also undergo metabolic alterations, frequently adopting immunosuppressive phenotypes promote progression reduce efficacy therapies. The competition for essential nutrients, glucose, between cancer compromises functions effector cells, T cells. Additionally, by-products like lactate kynurenine further suppress activity populations, including regulatory M2 macrophages. Targeting glycolysis presents new opportunities overcome improve therapeutic outcomes GI cancers. Modulating these key has potential reinvigorate exhausted shift toward phenotypes, enhance effectiveness immunotherapies other treatments. Future strategies will require continued research into metabolism, development novel inhibitors, clinical trials evaluating combination Identifying validating biomarkers be crucial patient stratification treatment monitoring. Insights may have broader implications across multiple types, offering avenues improving treatment.

Language: Английский

Citations

1
Macrophage metabolism in nonalcoholic fatty liver disease DOI Creative Commons
Wenhui Zhang, Ren Lang

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

Published: Oct. 4, 2023

Nonalcoholic fatty liver disease (NAFLD) and its inflammatory often progressive subtype nonalcoholic steatohepatitis (NASH), have emerged as significant contributors to hepatic morbidity worldwide. The pathophysiology of NAFLD/NASH is multifaceted, variable, remains incompletely understood. pivotal role liver-resident recruited macrophages in the pathogenesis NAFLD NASH widely acknowledged a crucial factor innate immunity. remarkable plasticity enables them assume diverse activation polarization states, dictated by their immunometabolism microenvironment functional requirements. Recent studies field elucidated that alterations metabolic profile can profoundly influence state functionality, thereby influencing various pathological processes. This review primarily focuses on elucidating states macrophages, highlighting correlation between characteristics transition from pro-inflammatory anti-inflammatory phenotypes. Additionally, we explore potential targeting macrophage metabolism promising therapeutic approach for management NAFLD/NASH.

Language: Английский

Citations

16
Prognostic Value of Monocarboxylate Transporter 1 Overexpression in Cancer: A Systematic Review DOI Open Access
Ana Silva, Mónica Cerqueira,

B. Rosa

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5141 - 5141

Published: March 7, 2023

Energy production by cancer is driven accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate shuttled to and from cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer extruder lactate, being widely studied recent years generally associated with a aggressiveness phenotype. The aim this systematic review was assess the prognostic value immunoexpression different malignancies. Study collection performed searching nine databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web Science, OVID, TRIP PsycINFO), using keywords “cancer”, “Monocarboxylate transporter 1”, “SLC16A1” “prognosis”. Results showed that indicator poor prognosis decreased survival for patients sixteen types malignancies; associations between transporter’s overexpression larger tumour sizes, higher disease stage/grade metastasis occurrence were also frequently observed. Yet, correlated better outcomes colorectal cancer, pancreatic ductal adenocarcinoma non-small cell lung patients. These support applicability biomarker prognosis, although cohorts would be necessary validate overall role outcome predictor.

Language: Английский

Citations

14
Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance DOI Creative Commons
Rong Qin, Xirui Fan, Yun‐Wen Huang

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 50, P. 102156 - 102156

Published: Oct. 13, 2024

Language: Английский

Citations

4
Orchestrated immune responses to Mycobacterium marinum natural infection in tongue sole (Cynoglossus semilaevis) DOI
Yangzhen Li, Limin Song, Yan Xu

et al.

Fish & Shellfish Immunology, Journal Year: 2025, Volume and Issue: unknown, P. 110145 - 110145

Published: Jan. 1, 2025

Language: Английский

Citations

0
Leptin decreases Th17/Treg ratio to facilitate neuroblastoma via inhibiting long-chain fatty acid catabolism in tumor cells DOI Creative Commons
Meng Li, Di Li, Haiyun Wang

et al.

OncoImmunology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 4, 2025

The exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data mediastinal NB tissues, we found that the content long-chain acylcarnitine (LCAC) was increased positively associated leptin expression advanced Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg instead Th17 cells, benefited from cell proliferation, migration, drug resistance. Mechanically, blunted activity carnitine palmitoyltransferase 2 (CPT2), key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, depresses oxidative phosphorylation (OXPHOS) energy supply increases lactic acid (LA) production glycolysis modulate differentiation. These findings highlight excess contributes lipid metabolism dysfunction subsequently misdirects differentiation tumor micro-environment (TME), indicating targeting could be a strategy retarding progression.

Language: Английский

Citations

0
Metabolic reprogramming and signalling cross-talks in tumour–immune interaction: a system-level exploration DOI Creative Commons

Mudita Shukla,

Rupa Bhowmick, Piyali Ganguli

et al.

Royal Society Open Science, Journal Year: 2024, Volume and Issue: 11(3)

Published: March 1, 2024

Tumour-immune microenvironment (TIME) is pivotal in tumour progression and immunoediting. Within TIME, immune cells undergo metabolic adjustments impacting nutrient supply the anti-tumour response. Metabolic reprogramming emerges as a promising approach to revert response towards pro-inflammatory state conquer dominance. This study proposes immunomodulatory mechanisms based on employs regulatory flux balance analysis modelling approach, which integrates signalling, metabolism processes. For first time, comprehensive system-level model constructed capture signalling cross-talks during tumour-immune interaction constraints are incorporated by considering time lag between them. The identifies novel features enhance while suppressing activity. Particularly, altering exchange of succinate oxaloacetate glioma macrophage enhances cells. Inhibition glutamate uptake T-cells disrupts antioxidant mechanism reprograms metabolism. through adenosine monophosphate (AMP)-activated protein kinase (AMPK), coupled with inhibition, was identified most impactful combination restore T-cell function. A understanding gene regulation represents favourable promote cell recovery from

Language: Английский

Citations

3