Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression? DOI Open Access
X. H. Zhang, Lingbo Liu

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12550 - 12550

Published: Nov. 22, 2024

Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T senescence constitutes primary mechanism underlying in acute myeloid leukemia (AML) represents one potential causes immunotherapy failure. AML usually progresses rapidly is highly susceptible to drug resistance, thereby resulting recurrence patient mortality. Hence, disrupting interface within bone marrow microenvironment has emerged critical objective for synergistically enhancing tumor immunotherapy. In this review, we summarize general characteristics, distinctive phenotypes, regulatory signaling networks senescent cells highlight their clinical significance AML. Additionally, discuss therapeutic strategies alleviating reversing senescence.

Language: Английский

RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair DOI
Chun-Kai Huang, Zhiyong Chen,

Zhongxing Zhou

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 135(4), P. 518 - 536

Published: Aug. 2, 2024

Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt immune response of macrophages, which is critical to preserve homeostasis effective infarct repair, remain be fully defined. Here, we aimed determine ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses macrophages. We used transcriptome analysis mouse macrophages bone marrow-derived identify E3 ubiquitin ligase RNF149 (ring finger protein 149) as a modulator macrophage MI. Employing loss-of-function methodologies, marrow transplantation approaches, adenovirus-mediated overexpression elucidated functional role explored underlying through flow cytometry, analysis, immunoprecipitation/mass spectrometry experiments. expression was measured tissues patients with acute MI healthy controls. highly expressed murine human at early phase Knockout RNF149, Rnf149-/- marrow, macrophage-specific RNF149-knockdown markedly exacerbated dysfunction models. Conversely, attenuated ischemia-induced decline contractile function. deletion increased infiltration proinflammatory monocytes/macrophages, accompanied by hastened reparative subsets, leading aggravation apoptosis impairment healing. Our data revealed infiltrated restricted promoting ubiquitylation-dependent proteasomal degradation IFNGR1 (interferon gamma receptor 1). Loss rescued deleterious deficiency further demonstrated STAT1 (signal transducer activator transcription 1) activation induced Rnf149 transcription, which, turn, destabilized counteract type-II IFN (interferon) signaling, creating feedback control mechanism fine-tune macrophage-driven inflammation. These findings highlight significance molecular brake uncover macrophage-intrinsic posttranslational essential for maintaining facilitating

Language: Английский

Citations

4
Arginine and colorectal cancer: Exploring arginine-related therapeutic strategies and novel insights into cancer immunotherapies DOI
Ketao Jin, Xiufeng Chu, Jun Qian

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 148, P. 114146 - 114146

Published: Jan. 28, 2025

Language: Английский

Citations

0
Single‐cell RNA Sequencing Contributes to the Treatment of Acute Myeloid Leukaemia With Hematopoietic Stem Cell Transplantation, Chemotherapy, and Immunotherapy DOI

Raed Obaid Saleh,

Ahmed Hjazi,

Safia Obaidur Rab

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(4)

Published: April 1, 2025

ABSTRACT Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of blasts, as well transcriptional/epigenetic alterations impaired apoptosis, all which lead to excessive proliferation malignant blood cells in the bone marrow. It these mutations that cause tumor heterogeneity, linked a higher risk relapse death makes anti‐AML treatments like HSCT, chemotherapy, immunotherapy (ICI, CAR T‐cell‐based therapies, cancer vaccines) less effective. Single‐cell RNA sequencing (scRNA‐seq) also it possible find cellular subclones profile tumors, opens up new diagnostic therapeutic targets for better AML management. The HSCT process works when genetic transcriptional information about patient donor stem collected. This saves time lowers harmful side effects happening body.

Language: Английский

Citations

0
Development of Novel Silicon-Based Hydrophobic Tags (SiHyT) for Targeted Proteins Degradation DOI

Ma Lan,

Kun Zhang, Ziqi Huang

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

Recent advances in targeted protein degradation (TPD) have propelled it to the forefront of small molecular drug discovery. Among these, hydrophobic tagging (HyT) strategies garnered significant interest. Carbon-based tags been recognized as effective Hyts for degrading a variety target proteins. In this study, we introduce novel class potential EGFR degraders first time, which combine Gefitinib with silicon-based (SiHyT). The most promising candidate, degrader 7, links simple TBDPS silyl ether, has shown efficacy mutant EGFRs via ubiquitin-proteosome system (UPS) both vitro and vivo. Notably, 7 exhibits enhanced oral bioavailability owing its superior metabolic stability compared traditional carbon-based Hyts. Mechanistically, was revealed that disrupts by dissociating EGFR-HSP90 complex recruiting E3 ligase, RNF149. More importantly, potent selective PD-L1 BTK were discovered successfully utilizing SiHyT strategy. development these innovative compounds could broaden repertoire HyTs, enhancing future design TPD agents.

Language: Английский

Citations

3
High-dimensional deconstruction of ovarian cancer at single-cell precision reveals HEBP2 that reshape the TIME and drive carboplatin resistance DOI Creative Commons
Bikang Yang, Miao Dai

Translational Oncology, Journal Year: 2024, Volume and Issue: 44, P. 101917 - 101917

Published: March 29, 2024

Single-cell sequencing was employed to analyze the tumor immune microenvironment in ovarian cancer (OC) patients, exploring evolutionary roles of various macrophage subgroups OC progression and their correlation with fatty acid metabolism-related genes contributing drug resistance.

Language: Английский

Citations

1
Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression? DOI Open Access
X. H. Zhang, Lingbo Liu

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12550 - 12550

Published: Nov. 22, 2024

Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T senescence constitutes primary mechanism underlying in acute myeloid leukemia (AML) represents one potential causes immunotherapy failure. AML usually progresses rapidly is highly susceptible to drug resistance, thereby resulting recurrence patient mortality. Hence, disrupting interface within bone marrow microenvironment has emerged critical objective for synergistically enhancing tumor immunotherapy. In this review, we summarize general characteristics, distinctive phenotypes, regulatory signaling networks senescent cells highlight their clinical significance AML. Additionally, discuss therapeutic strategies alleviating reversing senescence.

Language: Английский

Citations

0