Exosomes target HBV-host interactions to remodel the hepatic immune microenvironment

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 5, 2024

Chronic hepatitis B poses a significant global burden, modulating immune cells, leading to chronic inflammation and long-term damage. Due its hepatotropism, the virus (HBV) cannot infect other cells. The mechanisms underlying intercellular communication among different liver cells in HBV-infected individuals microenvironment imbalance remain elusive. Exosomes, as important cargo transportation tools between hepatocytes have been shown assist HBV regulate microenvironment. However, role of exosomes has only gradually received attention recent years. Minimal literature systematically elaborated on reshaping liver. This review unfolds sequentially based biological processes exosomes: exosomes' biogenesis, release, transport, uptake by recipient their impact We delineate how influences biogenesis exosomes, utilizing exosomal covert transmission, reshapes hepatic And characteristics functions potential applications are summarized predicted.

Language: Английский

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A six lipid metabolism related gene signature for predicting the prognosis of hepatocellular carcinoma

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 1, 2022

Abstract Globally, hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors. Studies have shown that alterations in tumor immune microenvironment (TIME) play a significant role pathogenesis and progression HCC, notably, lipid metabolism has been to regulate TIME. Therefore, predicting prognosis efficacy immunotherapy patients with metabolism-related prognostic factors are highly relevant. mRNA expression data HCC were obtained from Cancer Genome Atlas (TCGA), International Consortium (ICGC), gene omnibus (GEO) databases. genes also GSEA Least absolute shrinkage selection operator regression analysis, univariate multivariate Cox proportional hazards analysis used explore further construct signature training set, ICGC GSE54236 validate accuracy signature. qRT-PCR was detect levels tissues their paired adjacent tissues. Nile red staining demonstrate content Immunofluores-cence ELISA cells responses serum. Six (ADH1C, APEX1, ME1, S100A10, ACACA CYP2C9) identified as independent factors, which for risk model construction patients. The areas under 1-, 2-, 3-year ROC curves TCGA cohort 0.758, 0.701 0.671, respectively. Compared paracancerous tissues, revealed S100A10 up-regulated whereas ADH1C CYP2C9 down-regulated indicated this study showed both tissue serum high-risk group exhibited accumulation. Our comprising six could provide survival prediction. Moreover, drug therapy target molecular marker research can be guided by our predictive model.

Language: Английский

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Antitumor effects of natural killer cells derived from gene-engineered human-induced pluripotent stem cells on hepatocellular carcinoma

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 4, 2025

Abstract Mortality and recurrence rates of hepatocellular carcinoma (HCC) remain high despite the use various treatment methods. Recently, cell-based immunotherapy using natural killer (NK) cells has attracted considerable attention in cancer immunotherapy. NK generated from induced pluripotent stem (iPSCs) are a new option for as an cell resource. The eNK (HLCN061, developed by HEALIOS K.K.) human iPSC-derived differentiated clinical-grade iPSCs which IL-15, CCR2B, CCL19, CD16a, NKG2D have been introduced. In this study, we aimed to evaluate potential therapy HCC treatment. analysis surface intracellular molecules revealed that antitumor-related (TRAIL, CD226, CD16) cytotoxic factors (perforin, granzyme B, TNFα, IFNγ) were highly expressed. addition, exhibited cytotoxicity against lines (HepG2, HuH7, SNU-423), sensitive NKG2D, TRAIL, CD226. TRAIL perforin/granzyme B pathways largely involved mechanism, indicated reduction inhibitory antibodies concanamycin A, inhibits B-mediated cytotoxicity. Our data suggest cells, whose functions enhanced genetic engineering, improve

Language: Английский

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Uncovering the heterogeneity of NK cells on the prognosis of HCC by integrating bulk and single-cell RNA-seq data

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 18, 2025

The tumor microenvironment (TME) plays a critical role in the development, progression, and clinical outcomes of hepatocellular carcinoma (HCC). Despite natural killer (NK) cells immunity, there is limited research on their status within HCC. In this study, single-cell RNA sequencing (scRNA-seq) analysis HCC datasets was performed to identify potential biomarkers investigate involvement TME. Single-cell data were extracted from GSE149614 dataset processed for quality control using "Seurat" package. subtypes TCGA classified through consensus clustering based differentially expressed genes (DEGs). Weighted gene co-expression network (WGCNA) employed construct networks. Furthermore, univariate multivariate Cox regression analyses conducted variables linked overall survival. single-sample set enrichment (ssGSEA) used analyze immune screened genes. A total 715 DEGs 864 identified, with 25 overlapping found between two datasets. prognostic risk score model then established. Significant differences cell infiltration observed high-risk low-risk groups. Immunohistochemistry showed that HRG expression decreased compared normal tissues, whereas TUBA1B elevated Our study identified two-gene signature NK markers highlighted TME, which may offer novel insights immunotherapy strategies. Additionally, we developed an accurate reliable model, combining factors aid clinicians decision-making.

Language: Английский

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Beyond Adaptive Immunity: Trained Innate Immune Responses as a Novel Frontier in Hepatocellular Carcinoma Therapy

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1250 - 1250

Published: April 7, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, with the majority cases detected at advanced stages when curative options are limited. Current systemic therapies, including immune checkpoint inhibitors, demonstrate limited efficacy durable responses in only 15-20% patients. This poor response largely attributed to HCC's immunosuppressive microenvironment, which blunts effective T-cell responses. By illustrating that innate cells can acquire memory-like characteristics through process known as trained immunity, recent evidence has challenged conventional belief immunity devoid memory. review investigates potential defined by long-term functional reprogramming epigenetic, transcriptomic, and metabolic changes, provide new therapeutic opportunities for HCC. We discuss mechanisms transform HCC enhanced inflammatory cytokine production, repolarization tumor-associated macrophages toward anti-tumor phenotypes, increased cell infiltration, improved bridging adaptive immunity. further evaluate emerging strategies leveraging principles, BCG vaccination, β-glucan administration, cytokine-trained NK therapy, innovative combination approaches. Finally, we address resistance future directions clinical application. integrating into immunotherapeutic regimens, may significantly improve outcomes patients, potentially transforming disease more manageable condition.

Language: Английский

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The Important Roles of Natural Killer Cells in Liver Fibrosis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1391 - 1391

Published: May 8, 2023

Liver fibrosis accompanies the development of various chronic liver diseases and promotes their progression. It is characterized by abnormal accumulation extracellular matrix proteins (ECM) impaired ECM degradation. Activated hepatic stellate cells (HSCs) are major cellular source ECM-producing myofibroblasts. If uncontrolled, it may lead to cirrhosis even cancer, primarily hepatocellular carcinoma (HCC). Natural killer (NK) a key component innate immunity have miscellaneous roles in health disease. Accumulating evidence shows that NK play dual progression fibrosis, including profibrotic anti-fibrotic functions. Regulating can suppress activation HSCs improve cytotoxicity against activated or myofibroblasts reverse fibrosis. Cells such as regulatory T (Tregs) molecules prostaglandin E receptor 3 (EP3) regulate cytotoxic function cells. In addition, treatments alcohol dehydrogenase (ADH3) inhibitors, microRNAs, natural group 2, member D (NKG2D) activators, products enhance cell inhibit this review, we summarized molecular factors affect interaction with HSCs, well Despite lot information about our current knowledge still insufficient explain complex crosstalk between these hepatocytes, sinusoidal endothelial cells, Kupffer B thrombocytes, regarding

Language: Английский

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Biomaterial-Mediated Exogenous Facile Coating of Natural Killer Cells for Enhancing Anticancer Efficacy toward Hepatocellular Carcinoma

Bioconjugate Chemistry, Journal Year: 2023, Volume and Issue: 34(10), P. 1789 - 1801

Published: Sept. 20, 2023

Natural killer (NK) cells exhibit a good therapeutic efficacy against various malignant cancer cells. However, the of plain NK is relatively low due to inadequate selectivity for Therefore, enhance targeting and anticancer cells, we have rationally designed biomaterial-mediated ex vivo surface engineering technique membrane decoration recognition ligands onto Our lipid conjugate biomaterial contains three major functional moieties: (1) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) cell anchoring, (2) polyethylene glycol intracellular penetration blocker, (3) lactobionic acid (LBA) recognition. The was successfully applied surfaces (LBA-NK) functionalities, especially toward asialoglycoprotein receptor (ASGPR)-overexpressing hepatocellular carcinoma. Highly efficient homogeneous editing achieved with simple coating process while maintaining intrinsic properties LBA-NK showed potential ASGPR-mediated tumor binding (through LBA-ASGPR interaction) thereby significantly augmented efficacies HepG2 liver Thus, can be novel strategy treatment cancers via facilitated immune synapse interactions in comparison currently available therapies.

Language: Английский

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Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 10, 2024

HBV infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC), highly invasive tumor, characterized by its persistent immunosuppressive microenvironment. This review provides an in-depth analysis HBV-related HCC explores interactions between neutrophils, natural killer cells, dendritic examining their roles in regulating tumor-associated macrophages CD8+ T cells shaping tumor Two critical players milieu are (TAMs). The study how TAMs, initially recruited to combat infection, transform, adopting tumor-promoting phenotype, turning against body, promoting cell proliferation, suppressing anti-tumor immunity, assisting spread cancer. Meanwhile, crucial controlling become dysfunctional exhausted response chronic viral inflammation. then dissects TAMs manipulate this immune response, further depleting functions through mechanisms like arginine deprivation creating hypoxic environments that lead exhaustion. Finally, it challenges promising therapeutic avenues target either separately or combination with antiviral therapy personalized medicine approaches, offering hope improved outcomes HCC.

Language: Английский

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The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: Nov. 22, 2022

Abstract Acute liver failure caused by drug overdose is a significant clinical problem in developed countries. Acetaminophen (APAP), widely used analgesic and antipyretic drug, but its can cause acute failure. In addition to APAP-induced direct hepatotoxicity, the intracellular signaling mechanisms of injury (AILI) including metabolic activation, mitochondrial oxidant stress proinflammatory response further affect progression severity AILI. Liver inflammation result multiple interactions cell death molecules, immune cell-derived cytokines chemokines, as well damaged cell-released signals which orchestrate hepatic infiltration. The immunoregulatory interplay these inflammatory mediators switching responses during AILI lead different fate pathology. Thus, better understanding complex subsets experimental models defining their functional involvement disease are essential identify novel therapeutic targets for treatment Here, this present review aims systematically elaborate on underlying immunological AILI, relevance cells effector briefly discuss great potential based mediators.

Language: Английский

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Machine learning-based prognostic modeling of lysosome-related genes for predicting prognosis and immune status of patients with hepatocellular carcinoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 19, 2023

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Lysosomes are organelles that play an important role in cancer progression by breaking down biomolecules. However, the molecular mechanisms lysosome-related genes HCC not fully understood.

Language: Английский

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