Frontiers in Oncology, Год журнала: 2024, Номер 14
Опубликована: Ноя. 28, 2024
Gastric cancer (GC) is a malignant tumor associated with significant rates of morbidity and mortality. Hence, developing efficient predictive models directing clinical interventions in GC crucial. Lactylation proteins detected gastric tumors linked to the advancement cancer.
Язык: Английский
Cancer Communications, Год журнала: 2024, Номер 44(11), С. 1231 - 1260
Опубликована: Сен. 2, 2024
Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles tumors, their impact on tumor immunology unclear. This study aimed to elucidate the role SRSF10 HCC immunotherapy. Methods To identify key genes associated immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, Cancer Genome Atlas Gene Expression Omnibus database analyses. We investigated biological functions evasion using vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, patient‐derived organotypic spheroids. Results was upregulated tumors poor prognosis. Moreover, positively regulated lactate production, SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop cells. Increased levels promoted M2 macrophage polarization, thereby inhibiting CD8 + T cell activity. Mechanistically, interacted 3′‐untranslated region MYB , enhancing stability, subsequently upregulating glycolysis‐related enzymes including glucose transporter 1 ( GLUT1 ), hexokinase HK1 dehydrogenase A LDHA resulting elevated intracellular extracellular levels. Lactate accumulation induced lactylation, which further expression. Additionally, produced by H3K18la site upon transport into macrophages, activating transcription pro‐tumor turn, inhibited enrichment cells proportion interferon‐γ microenvironment (TME), thus creating an immunosuppressive TME. Clinically, could serve as biomarker for assessing resistance solid tumors. Pharmacological targeting selective inhibitor 1C8 enhanced programmed death (PD‐1) monoclonal antibodies (mAbs) both murine human preclinical models. Conclusions SRSF10/MYB/glycolysis/lactate axis is critical triggering anti‐PD‐1 resistance. Inhibiting may overcome tolerance HCC.
Язык: Английский
Процитировано
22
Clinical Science, Год журнала: 2025, Номер 139(02), С. 151 - 169
Опубликована: Янв. 1, 2025
Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.
Язык: Английский
Процитировано
1
Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)
Опубликована: Март 7, 2025
Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.
Язык: Английский
Процитировано
1
Theranostics, Год журнала: 2025, Номер 15(5), С. 1787 - 1821
Опубликована: Янв. 2, 2025
Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.
Язык: Английский
Процитировано
0
Life Sciences, Год журнала: 2025, Номер 363, С. 123395 - 123395
Опубликована: Янв. 13, 2025
Язык: Английский
Процитировано
0
Advances in Clinical Medicine, Год журнала: 2025, Номер 15(01), С. 981 - 989
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)
Опубликована: Янв. 22, 2025
Osteosarcoma is the most common malignant bone tumor in children and adolescents, characterized by high disability mortality rates. Over past three decades, therapeutic outcomes have plateaued, underscoring critical need for innovative targets. Solute carrier (SLC) family transporters been implicated progression of a variety tumors, however, their specific role osteosarcoma remains poorly understood. The single-cell sequencing data from GSE152048 GSE162454, along with RNA-seq TARGET GSE21257 cohorts, were utilized analysis this study. LASSO regression was conducted to identify prognostic genes construct an SLC-related signature. Survival ROC evaluated validity ESTIMATE CIBERSORT Packages assess immune infiltration status. Pseudotime CellChat analyses performed investigate relationship between SLC7A1, phenotypes, microenvironment. CCK8 assays, EdU staining, colony formation Transwell co-culture systems used effects SLC7A1 on cell proliferation, metastasis, macrophage polarization. Finally, virtual docking identified potential drugs targeting SLC7A1. SLCs displayed distinct expression patterns across various types within microenvironment, myeloid cells exhibiting preference amino acid uptake. A model comprising nine constructed via regression, showing highest hazard ratio. Multiple analytical algorithms indicated that associated checkpoint gene expression. Single-cell predominantly expressed correlated characteristics. also regulate interactions macrophages, as well modulate function through multiple pathways. In vitro assays survival demonstrated inhibition suppressed phenotype cells, correlating poor prognosis. Co-culture models confirmed involvement screening CETSA Cepharanthine inhibitors signatures can be evaluation osteosarcoma. Pharmacological may feasible approach
Язык: Английский
Процитировано
0
Biomedicine & Pharmacotherapy, Год журнала: 2025, Номер 184, С. 117934 - 117934
Опубликована: Фев. 21, 2025
Язык: Английский
Процитировано
0
Cancer Drug Resistance, Год журнала: 2025, Номер unknown
Опубликована: Фев. 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.
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер 1872(4), С. 119927 - 119927
Опубликована: Фев. 28, 2025
Язык: Английский
Процитировано
0