Integration of single-cell and spatial transcriptomics reveals fibroblast subtypes in hepatocellular carcinoma: spatial distribution, differentiation trajectories, and therapeutic potential

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 18, 2025

Language: Английский

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The fibroinflammatory response in cancer

Nature reviews. Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Sophisticated roles of tumor microenvironment in resistance to immune checkpoint blockade therapy in hepatocellular carcinoma

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

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Comprehensive Analyses of Single-Cell and Bulk RNA Sequencing Data From M2 Macrophages to Elucidate the Immune Prognostic Signature in Patients with Gastric Cancer Peritoneal Metastasis

ImmunoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 14, P. 383 - 402

Published: April 1, 2025

The peritoneum is a common site of metastasis in gastric cancer (GC), associated with poor prognosis and significant morbidity. proclivity GCs to metastasize the has been hypothesized occur due latter's immunosuppressive microenvironment, such as stromal infiltration M2 macrophage enrichment, which are increased risk PM. As far we know, model that can effectively predict patients GCPM still lacking. Consequently, constructed prognostic based on macrophages peritoneal metastasis, aiming enhance predictive precision guide tailored therapeutic interventions. macrophage-associated genes were identified combination marker from single-cell RNA sequencing (scRNA-seq) modular weighted gene coexpression network analysis (WGCNA). A was via LASSO validated internal external cohorts. We further compared immune checkpoints, chemotherapeutic drug sensitivity between patient groups stratified by clarify landscape GCPM. Our study 38 macrophage-related bulk sequencing. developed expression levels 4 signature genes: DAB2, SPARC, PLTP, FOLR2. feasibility validation sets (TCGA, GSE62254 IMvigor210). also supported prediction results basis immunohistochemical results. Notably, higher scores had lower proportion MSI-H TMB, prevalence stages III-IV, likelihood responding favorably immunotherapy. could response chemo-immune therapy score promising independent factor closely correlated microenvironment clinicopathological characteristics.

Language: Английский

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Crosstalk between exosomes and tumor-associated macrophages in hepatocellular carcinoma: implication for cancer progression and therapy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, represents a significant cause cancer-related mortality. While our understanding its pathogenesis is comparatively comprehensive, influence tumor microenvironment (TME) on progression warrants additional investigation. Tumor-associated macrophages (TAMs) have impacts cancer cell proliferation, migration, invasion, and immune response, facilitating complex interaction within TME. Exosomes, which measure between 30 150 nanometers in size, are categorized into small extracellular vesicles, secreted by wide range eukaryotic cells. They can transfer biological molecules including proteins, non-coding RNAs, lipids, mediates intercellular communication Emerging evidence has revealed that exosomes regulate macrophage polarization, thus impacting responses TME HCC. Moreover, TAM-derived also play crucial roles malignant transformation, hold immense potential for therapy. In this review, we elaborate crosstalk TAMs during HCC development. delve feasible treatment approaches therapy emphasize limitations challenges translation derived from clinical courses therapy, may provide new perspectives further ameliorations therapeutic regimes based to advance their applications.

Language: Английский

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High Fibroblast Activation Protein Expression in Hepatocellular Carcinoma: CT Imaging Features and Histological Characteristics

Academic Radiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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CD163⁺/Dab2⁺Macrophages Alleviate Cardiac Hypertrophy via Nrg2/ErbB4-Mediated Mitochondrial Reprogramming

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 26, 2025

ABSTRACT Background Pathological cardiac hypertrophy is a hallmark of numerous cardiovascular diseases, yet effective targeted therapies remain elusive in current clinical practice. Cardiac macrophages contribute to disease progression, but the underlying mechanisms have not been fully elucidated. Methods Single-nucleus RNA-sequencing, bulk proteomics, metabolomics, and mouse model pressure overload were employed investigate remodeling. We identified macrophage subset co-expressing CD163 Dab2 examined its role using immunofluorescence, flow cytometry, functional assays. further assessed Nrg2/ErbB4 signaling axis through genetic pharmacological modulation. Results CD163⁺/Dab2⁺ reduced hypertrophic hearts positively correlated with Nrg2 expression. These alleviated cardiomyocyte vitro, an effect abolished by knockdown. In vivo, recombinant treatment mitigated hypertrophy, preserved mitochondrial structure, restored bioenergetics via ErbB4 receptor. Transcriptomic analyses confirmed enhanced expression genes involved oxidative phosphorylation. Furthermore, + /Dab2 improved dysfunction pathway vitro. Conclusions that protects against pathological promoting function signaling. This may offer promising therapeutic target for interventions hypertrophy.

Language: Английский

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The regulatory effects and applications of TIGIT/CD155 on the tumor microenvironment in HCC

View, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Abstract Hepatocellular carcinoma (HCC) is the most commonly occurring liver cancer, and poses a significant burden on individuals, society, economy, healthcare system. Despite advancements in therapeutic options such as surgical interventions targeted therapies, complex etiology clinical presentations of cancer continue to result suboptimal treatment responses. Therefore, identifying more effective methods has become priority HCC research. Targeting programmed cell death protein 1 with immune checkpoint inhibitors significantly improved outcomes; however, these drugs are still limited by their efficacy risk immune‐related adverse reactions, which can death. TIGIT, newly emerging checkpoint, provides novel focus for immunotherapy. The TIGIT/CD155 axis actively reprograms tumor microenvironment (TME), driving carcinogenesis, evasion, metastatic spread. This review systematically elucidates dynamic regulatory networks biological impacts TME, while evaluating its potential through two exploratory strategies: (i) TIGIT have augment anticancer PD‐1/PD‐L1 blockade, (ii) combination regimens integrating TIGIT‐targeted therapies antibody–drug conjugates (ADCs) or chimeric antigen receptor macrophages (CAR‐Ms) could represent viable approach overcoming limitations inherent monotherapy.

Language: Английский

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New Relevant Evidence in Cholangiocarcinoma Biology and Characterization

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4239 - 4239

Published: Dec. 19, 2024

Among solid tumors, cholangiocarcinoma (CCA) emerges as one of the most difficult to eradicate. The silent and asymptomatic nature this tumor, particularly in its early stages, well high heterogeneity at genomic, epigenetic, molecular levels delay diagnosis, significantly compromising efficacy current therapeutic options thus contributing a dismal prognosis. Extensive research has been conducted on pathobiology CCA, recent advances have made classification characterization new targets. Both targeted therapy immunotherapy emerged effective safe strategies for various types cancers, demonstrating potential benefits advanced CCA. Furthermore, deeper comprehension cellular components tumor microenvironment (TME) opened up possibilities innovative treatment methods. This review discusses evidence biology highlighting novel possible druggable

Language: Английский

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