DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy DOI Creative Commons
Yixun Li, Chong Guo,

Fujia Zhang

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Dec. 20, 2024

Acute myeloid leukemia (AML) is a common hematological tumor, but it difficult to treat. DNMT1 DNA methyltransferase whose main function maintain stable methylation during the replication process. also plays an important role in AML, its cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear. In this study, we isolated primary NK cells from peripheral blood of healthy volunteers and AML patients treated them with 10 ng/mL IL-12, 50 IL-15 IL-18 promote their differentiation into CIML cells. The was evaluated by RT‒qPCR, western blotting, ELISAs, flow cytometry. highly expressed patients. Knocking down significantly increased expression CD25, CD137, CD107a, IFN-γ, TNF-α Mechanistically, knocking promoted autophagy activating AMPK/mTOR signaling pathway, thereby enhancing alleviating progression AML. Our study revealed that downregulation DNMT may be new target for treatment

Language: Английский

No time to die: Epigenetic regulation of natural killer cell survival DOI
Leen Hermans, Timothy E. O’Sullivan

Immunological Reviews, Journal Year: 2024, Volume and Issue: 323(1), P. 61 - 79

Published: March 1, 2024

Summary NK cells are short‐lived innate lymphocytes that can mediate antigen‐independent responses to infection and cancer. However, studies from the past two decades have shown acquire transcriptional epigenetic modifications during inflammation result in increased survival lifespan. These findings blur lines between adaptive arms of immune system, suggest homeostatic mechanisms govern persistence malleable. Indeed, recent undergo continuous strictly regulated adaptations controlling their development, tissue residency, following inflammation. In this review, we summarize our current understanding critical factors regulating cell throughout lifespan, with a specific emphasis on regulate various contexts. A precise molecular will be important enhance therapies for cancer infectious diseases.

Language: Английский

Citations

3
Therapeutic potential of natural killer cells in neuroimmunological diseases DOI Creative Commons
Qing Zhang, Jing Lin, Mengge Yang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116371 - 116371

Published: March 2, 2024

Natural killer (NK) cells, a major component of the innate immune system, have prominent immunoregulatory, antitumor proliferation, and antiviral activities. NK cells act as double-edged sword with therapeutic potential in neurological autoimmunity. Emerging evidence has identified are involved development progression neuroimmunological diseases such multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalitis, Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, idiopathic myopathy. However, regulatory mechanisms functional roles highly variable different clinical states need to be further determined. In this review, we summarize for heterogenic involvement above conditions. Further, describe cutting-edge NK-cell-based immunotherapy preclinical highlight challenges that must overcome fully realize cells.

Language: Английский

Citations

3
LST1 expression correlates with immune infiltration and predicts poor prognosis in acute myeloid leukemia DOI Creative Commons
Haitao Xu, Dangui Chen,

Jia Lu

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 12, 2025

Clinical management of acute myeloid leukemia (AML) poses significant challenges due to its poor prognosis and heterogeneous nature. Discovering new biomarkers is crucial for improving risk assessment customizing treatment approaches. While leukocyte-specific transcript 1 (LST1) implicated in inflammation immune regulation, function AML remains ambiguous. In this investigation, we conduct a comprehensive investigation into LST1 expression profiles, clinical implications, functional pathways, interactions AML, leveraging multi-omics data experimental validations. Our examination shows increased levels when compared regular hematopoietic tissues, discovery validated by RT-qPCR Western blot analyses separate group. Elevated correlate with distinct clinicopathological features, including white blood cell counts, non-M3 FAB subtype, intermediate/poor cytogenetic risk. Importantly, heightened predict unfavorable overall survival outcomes across various subgroups, independently age We develop an integrative nomogram incorporating expression, demonstrating robust prognostic efficacy patient survival. Transcriptomic profiling identifies 275 differentially expressed genes between LST1-high -low cases, enriched cytokine signaling, modulation, adhesion, oncogenic pathways. Furthermore, exhibits associations the infiltration diverse subsets within microenvironment, particularly cells regulatory T (Tregs). conclusion, our study establishes as novel indicator immunological relevance emphasizing potential therapeutic implications. Further mechanistic elucidation pathogenesis translation.

Language: Английский

Citations

0
Identification of a novel cellular senescence-related lncRNA signature for prognosis and immune response in osteosarcoma DOI Open Access
Honglin Wu,

Chuanbao Deng,

Xiaoqing Zheng

et al.

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(7), P. 3742 - 3759

Published: July 1, 2024

Background: Cellular senescence, a novel hallmark of cancer, is associated with patient outcomes and tumor immunotherapy. However, at present, there no systematic study on the use cellular senescence-related long non-coding RNAs (CSR-lncRNAs) to predict survival in patients osteosarcoma. In this study, we aimed identify CSR-lncRNAs signature evaluate its potential as prognostic marker predictive tool for immune response Methods: We downloaded cohort osteosarcoma from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. performed differential expression co-expression analyses CSR-lncRNAs. univariate multivariate Cox regression along random forest algorithm lncRNAs significantly correlated senescence. Subsequently, assessed models using curves, receiver operating characteristic nomograms, C-index, decision curve analysis. Based model, were divided into two groups according their risk scores. Then, Ontology Kyoto Encyclopedia Genes Genomes analyses, compared clinical characteristics uncover functional differences. further conducted infiltration estimation stromal cells malignant tissues data (ESTIMATE), cell-type identification by estimating relative subsets rna transcripts (CIBERSORT), single-sample gene set enrichment analysis groups. also evaluated target genes checkpoint inhibitors (ICIs). Results: identified six that senescence accordingly established lncRNA incorporating these lncRNAs. nomogram indicated model was an independent factor could This demonstrated high accuracy upon validation. Further revealed low-risk group exhibited better enhanced infiltration. Conclusions: six-CSR-lncRNA effectively predicted might have improved

Language: Английский

Citations

2
Nature Killer Cell for Solid Tumors: Current obstacles and prospective remedies in NK cell therapy and beyond DOI
Jia‐Hao Tao, Jun Zhang, Huashun Li

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 205, P. 104553 - 104553

Published: Nov. 7, 2024

Language: Английский

Citations

2
DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy DOI Creative Commons
Yixun Li, Chong Guo,

Fujia Zhang

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 52(1)

Published: Dec. 20, 2024

Acute myeloid leukemia (AML) is a common hematological tumor, but it difficult to treat. DNMT1 DNA methyltransferase whose main function maintain stable methylation during the replication process. also plays an important role in AML, its cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear. In this study, we isolated primary NK cells from peripheral blood of healthy volunteers and AML patients treated them with 10 ng/mL IL-12, 50 IL-15 IL-18 promote their differentiation into CIML cells. The was evaluated by RT‒qPCR, western blotting, ELISAs, flow cytometry. highly expressed patients. Knocking down significantly increased expression CD25, CD137, CD107a, IFN-γ, TNF-α Mechanistically, knocking promoted autophagy activating AMPK/mTOR signaling pathway, thereby enhancing alleviating progression AML. Our study revealed that downregulation DNMT may be new target for treatment

Language: Английский

Citations

0