Comprehensive analysis reveals the tumor suppressor role of macrophage signature gene FCER1G in hepatocellular carcinoma

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 1, 2025

Hepatocellular carcinoma (HCC) progression is closely linked to the role of macrophages. This study utilized single-cell RNA sequencing and genomic analysis explore characteristic genes macrophages in HCC their impact on patient prognosis. We obtained se-quencing data from seven samples GEO database. Through principal component t-SNE dimensionality reduction, we identified 2,000 highly variable per-formed clustering annotation 17 cell clusters, revealing 482 macrophage-related feature genes. A LASSO regression model based these was developed predict prognosis patients, with validation TCGA-LIHC cohort demonstrating accuracy (AUC = 0.78, 0.72, 0.71 for 1-, 3-, 5-year survival rates, respectively). Additionally, patients high-risk group exhibited elevated tumor stemness scores, although no significant differences were observed microsatellite instability (MSI) mutational burden (TMB) scores. Immune-related analyses revealed that FCER1G expression downregulated associated key pathways such as apoptosis ferroptosis. Reduced significantly affected proliferation migration. Our prognostic provides new insights into precision immunotherapy holds implications future clinical applications.

Язык: Английский

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Nano-strategies for Targeting Tumor-Associated Macrophages in Cancer immunotherapy

Journal of Cancer, Год журнала: 2025, Номер 16(7), С. 2261 - 2274

Опубликована: Март 31, 2025

Tumor-associated macrophages (TAMs) are one type of the most abundant immune cells within tumor, resulting in immunosuppresive tumor microenvironment and resistance to immunotherapy. Thus, targeting TAMs is a promising therapeutic strategy for boosting cancer This study provides an overview current strategies TAMs, which focus on blocking recruitment by tumors, regulating polarization directly eliminating using various nanodrugs, especially with new categorization based specific signaling pathways, such as NF-κB, HIF-1α, ROS, STAT, JNK, PI3K, Notch involved their regulatory mechanism. The latest developments nanodrugs modulating these pathways discussed determining role microenvironment. Despite challenges clinical translation complexity nanodrug synthesis, potential enhancing effectiveness immunotherapy worthy expecting.

Язык: Английский

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Lactylation‐Driven NUPR1 Promotes Immunosuppression of Tumor‐Infiltrating Macrophages in Hepatocellular Carcinoma

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 30, 2025

While checkpoint immunotherapy effectively mobilizes T-cell responses against tumors, its success in hepatocellular carcinoma (HCC) is frequently undermined by immunosuppressive myeloid cells within the tumor microenvironment. This study investigates role of nuclear protein 1 (NUPR1), a gene prominently expressed tumor-associated macrophages (TAMs), mediating this suppression and influencing outcomes. Through comprehensive analysis single-cell RNA sequencing (scRNA-seq) datasets functional assays vitro vivo, NUPR1 identified as critical regulator TAMs. The upregulation associated with enhanced M2 macrophage polarization increased expression immune checkpoints PD-L1 SIRPA, resulting CD8+ T cell exhaustion diminished response to immunotherapy. Mechanistically, inhibits ERK JNK signaling pathways, thereby creating an milieu conducive progression. Additionally, tumor-derived lactate shown upregulate via histone lactylation, perpetuating feedback loop that intensifies suppression. Pharmacological targeting reverses polarization, curtails growth, augments efficacy PD-1 blockade preclinical models, positioning both potential biomarker for responsiveness therapeutic target boost HCC.

Язык: Английский

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Enhancing anti-angiogenic immunotherapy for melanoma through injectable metal–organic framework hydrogel co-delivery of combretastatin A4 and poly(I:C)

Nanoscale Advances, Год журнала: 2024, Номер 6(12), С. 3135 - 3145

Опубликована: Янв. 1, 2024

The interplay between vascularization and macrophage-induced immune suppression plays a crucial role in melanoma treatment. In this study, we propose novel combination approach to combat by simultaneously inhibiting tumor enhancing macrophage-mediated anti-tumor responses. We investigate the potential of combining combretastatin A4 (CA4), vascular-disrupting agent, with poly(I:C) (PIC), an immunostimulatory adjuvant. This effectively suppresses cell proliferation, disrupts vascularization, promotes macrophage polarization towards M1 phenotype for suppression. To facilitate efficient co-delivery CA4 PIC enhanced anti-angiogenic immunotherapy, develop injectable metal-organic framework hydrogel using Zeolitic Imidazolate Framework-8 (ZIF-8) hyaluronic acid (HA) (ZIF-8/HA). Our findings demonstrate that ZIF-8 enables loading enhances stability against RNAase degradation

Язык: Английский

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Phenotypic plasticity and increased infiltration of peripheral blood-derived TREM1+ mono-macrophages following radiotherapy in rectal cancer

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101887 - 101887

Опубликована: Янв. 1, 2025

Язык: Английский

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