The Ketogenic Diet Modulates Tumor-Associated Neutrophil Polarization via the AMOT-YAP/TAZ Axis to Inhibit Colorectal Cancer Progression DOI Creative Commons
Xiuwei Mi,

Yudong Duan,

Jiying Sun

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107494 - 107494

Published: Nov. 5, 2024

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), prognosis for late-stage patients remains poor, highlighting urgent need new preventive therapeutic strategies. Recent studies have focused on ketogenic diet (KD) its metabolite, β-hydroxybutyrate (BHB), their tumor-suppressive effects modulation inflammatory responses. Using azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced mouse CRC model, we found that BHB inhibit pro-tumor N2-type tumor-associated neutrophils (TANs) while promoting polarization TANs towards anti-tumor N1 type. This shift affects tumor growth metastasis. The underlying mechanism involves acting intracellular receptor histone deacetylases 3 (HDAC3), which modulates activation AMOT-YAP/TAZ axis, leading to inhibition pro-carcinogenic factor transcription release. Moreover, clinical cohort data corroborate these findings, showing with elevated levels significantly lower rates lymph node involvement, is associated a higher infiltration ratio anti-carcinogenic N1-type microenvironment (TME). These results suggest could serve as prognostic biomarker CRC. In conclusion, our findings indicate derived from KD regulates via HDAC3-AMOT-YAP/TAZ effectively inhibiting insights establish novel theoretical basis employing developing adjuvant immunotherapy strategy based neutrophils.

Language: Английский

Distinct Immunophenotypic Profiles and Neutrophil Heterogeneity in Colorectal Cancer DOI

Minghua Bai,

Yuzhao Jin,

Zihao Jin

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 616, P. 217570 - 217570

Published: Feb. 22, 2025

Language: Английский

Citations

1
GNGT1 remodels the tumor microenvironment and promotes immune escape through enhancing tumor stemness and modulating the fibrinogen beta chain-neutrophil extracellular trap signaling axis in lung adenocarcinoma DOI Open Access

Linlin Fan,

Xiaowei Wang, Xiu‐Mei Zhang

et al.

Translational Lung Cancer Research, Journal Year: 2025, Volume and Issue: 14(1), P. 239 - 259

Published: Jan. 1, 2025

Despite the recent advancements in treatment of cancer, 5-year survival patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. Lung adenocarcinoma (LUAD) is NSCLC's most common subtype, and metastasis major cause death cancer. Therefore, identifying novel targets associated NSCLC crucial to improving treatment. This study aimed characterize expression GNGT1 LUAD clarify mechanism underlying association between higher level worse prognosis patients. The transcriptome datasets clinical information were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database. Bioinformatics analyses performed 515 who stratified into two groups (high- low-GNGT1 group) according level. Overall survival, DNA promotor methylation, immune infiltration, gene set enrichment analysis (GSEA), Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway elucidate functions identify related hub genes LUAD. Their verified using tissues transgenic mice overexpressing under control a lung-specific promoter (Scgb1a1-Cre). was overexpressed poor prognosis. significantly correlated alteration hypomethylated status. High advanced lymph node degree infiltration. Functional indicated that differentially expressed (DEGs) high-GNGT1 group participated replication, replication preinitiation, M phase, while adhesion molecules, apoptosis, natural killer cell-mediated cytotoxicity all downregulated. Messenger RNA protein levels correspondingly regulated human Scgb1a1-Cre; LSL-GNGT1 mouse model (GNGT1fl/+ mice). tumor proliferation via enhancement stemness interaction driver genes. Elevated promoted epithelial-mesenchymal transformation, remodeled microenvironment, led metastasis, ultimately worsening survival-related

Language: Английский

Citations

0
Sophisticated roles of tumor microenvironment in resistance to immune checkpoint blockade therapy in hepatocellular carcinoma DOI Open Access
Yizhe Zhang, Yunshu Ma,

Ensi Ma

et al.

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

Published: Feb. 26, 2025

Hepatocellular carcinoma (HCC) remains a serious threat to global health, with rising incidence and mortality rates. Therapeutic options for advanced HCC are quite limited, the overall prognosis poor. Recent advancements in immunotherapy, particularly immune-checkpoint blockade (ICB) targeting anti-PD1/PD-L1 anti-CTLA4, have facilitated paradigm shift cancer treatment, demonstrating substantial survival benefits across various types, including HCC. However, only subset of patients exhibit favorable response ICB therapy, its efficacy is often hindered by development resistance. There many studies explore underlying mechanisms response. In this review, we compiled latest progression immunotherapies systematically summarized sophisticated which components tumor microenvironment (TME) regulate resistance therapy. Additionally, also outlined some scientific rationale strategies boost antitumor immunity enhance These insights may serve as roadmap future research help improve outcomes patients.

Language: Английский

Citations

0
A Reliable Prognostic Model for Hepatocellular Carcinoma Using Neutrophil extracellular traps and immune Related Genes DOI

Dahua Yuan,

Feng Zhang, Pengfei Lv

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Abstract Background Neutrophil extracellular traps (NETs) and immunity play critical roles in liver hepatocellular carcinoma (LIHC) progression, but their mechanisms remain unclear. This study explored the potential of NETs-related genes (NETs-RGs) immune-related (IRGs) as prognostic markers for LIHC. Methods LIHC transcriptome data IRGs were obtained from public databases, NETs-RGs derived prior research. Differentially expressed (DEGs) intersecting with key module identified, followed by Cox regression analysis machine learning to determine genes. A risk prediction model nomogram constructed validated. Enrichment analysis, immune infiltration, drug sensitivity studies conducted explore underlying mechanisms. Reverse transcription quantitative PCR (RT-qPCR) was used validate findings. Results Five genes—HMOX1, MMP9, TNFRSF4, MMP12, FLT3—were identified. demonstrated strong predictive ability. Gene set enrichment revealed pathways related retinol metabolism cytochrome P450 different groups. Immune infiltration showed regulatory T cells positively correlated MDSCs, which directly associated five Drug identified 74 drugs differential between groups; axitinib lower high-risk patients, while ABT-888 higher sensitivity. RT-qPCR confirmed reduced HMOX1 FLT3 expression tissues, MMP9 TNFRSF4 upregulated. Conclusion developed a robust prognosis, offering valuable insights clinical management personalized treatment strategies.

Language: Английский

Citations

0
Immune Checkpoint Inhibitors and Immunosuppressive Tumor Microenvironment: Current Challenges and Strategies to Overcome Resistance DOI
G. Gill,

Simmi Kharb,

Gitanjali Goyal

et al.

Immunopharmacology and Immunotoxicology, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 45

Published: May 16, 2025

Immune checkpoint inhibitors (ICIs) are shown to improve cancer treatment effectiveness by boosting the immune system of patient. Nevertheless, unique and highly suppressive TME poses a significant challenge, causing heterogeneity response or resistance in considerable number patients. This review focuses on evasive attributes TME. evasion mechanism include immunosuppressive cells, cytokine chemokine signaling, metabolic alterations overexpression molecules such as PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA their interactions within In addition, this overcoming targeting normalizing tumor blood vessels, blocking two three checkpoints simultaneously, combining vaccines, oncolytic viruses with ICIs other therapies. also necessity finding predictive markers for stratification patients check treatment. It remains be made certain new research intelligent innovations how these discoveries its interplay facilitate ICI change face

Language: Английский

Citations

0
Neutrophil extracellular traps in rheumatoid arthritis: Activating fibroblast-like synoviocytes via ATP citrate lyase DOI

Jun Li,

Xiaomin Wang, Min Tan

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113518 - 113518

Published: Nov. 12, 2024

Language: Английский

Citations

2
Global research trends and focus on the link between neutrophil extracellular traps and tumor: a bibliometric and visualization analysis from 2006 to 2024 DOI Creative Commons

Chaoyue Xiao,

Xiang Feng,

Zengyi Zhao

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 24, 2024

Background Neutrophil extracellular traps (NETs) have long been consistently considered an innate immune defense against foreign pathogens, but this oversimplified view has decelerated the progression of perceiving NET biology in chronic diseases. It is now increasingly accepted that NETs are not exclusive to anti-infection responses, also central players with a double-edged sword role cancer progression. gradually emerged as tumor diagnostic, predictive, and prognostic biomarkers, strenuous endeavors devoted tapping their potential new therapeutic targets. Correspondingly, boom studies on tumors recent years achieved series scientific outputs, which opens up perspective for sophisticated landscapes microenvironment. However, there still much room translate NET-targeted immunotherapies into clinical practice. Therefore, it necessary explore knowledge structure latent hotspots links between using bibliometric analysis. Methods publications from 2006 2024 were extracted Web Science Core Collection. Bibliometric analysis visualization conducted Microsoft Excel, VOSviewer, CiteSpace, R-bibliometrix. Results The included 1,339 authored by 7,747 scholars affiliated 1,926 institutions across 70 countries/regions relevant articles published 538 journals. Despite China’s maximum number publications, United States continued dominate field global cooperation center overwhelming citation counts. Frontiers Immunology most whereas Blood was cited journal. Wagner, Denisa D. Kaplan, Mariana J. concurrently both top 10 prolific authors author lists. Tumor microenvironment immunotherapy will likely be focus future research. Conclusions A comprehensive first map current landscape link hope providing guidance fresh perspectives further research field. promising antitumor targets, perhaps eventual destination realm

Language: Английский

Citations

1
The Ketogenic Diet Modulates Tumor-Associated Neutrophil Polarization via the AMOT-YAP/TAZ Axis to Inhibit Colorectal Cancer Progression DOI Creative Commons
Xiuwei Mi,

Yudong Duan,

Jiying Sun

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107494 - 107494

Published: Nov. 5, 2024

Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), prognosis for late-stage patients remains poor, highlighting urgent need new preventive therapeutic strategies. Recent studies have focused on ketogenic diet (KD) its metabolite, β-hydroxybutyrate (BHB), their tumor-suppressive effects modulation inflammatory responses. Using azoxymethane (AOM) / dextran sulfate sodium (DSS)-induced mouse CRC model, we found that BHB inhibit pro-tumor N2-type tumor-associated neutrophils (TANs) while promoting polarization TANs towards anti-tumor N1 type. This shift affects tumor growth metastasis. The underlying mechanism involves acting intracellular receptor histone deacetylases 3 (HDAC3), which modulates activation AMOT-YAP/TAZ axis, leading to inhibition pro-carcinogenic factor transcription release. Moreover, clinical cohort data corroborate these findings, showing with elevated levels significantly lower rates lymph node involvement, is associated a higher infiltration ratio anti-carcinogenic N1-type microenvironment (TME). These results suggest could serve as prognostic biomarker CRC. In conclusion, our findings indicate derived from KD regulates via HDAC3-AMOT-YAP/TAZ effectively inhibiting insights establish novel theoretical basis employing developing adjuvant immunotherapy strategy based neutrophils.

Language: Английский

Citations

1