Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma

Cancer Immunology Immunotherapy, Год журнала: 2024, Номер 73(3)

Опубликована: Фев. 13, 2024

Abstract T-cell receptor (TCR) engineered therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers potential solution, they empower T cells to induce ferroptosis and exert influence over the microenvironment. Atovaquone (ATO) stands prospective pharmaceutical candidate with target ferroptosis, effectively provoking an excessive generation accumulation reactive oxygen species (ROS). In this study, we evaluated effectiveness combination comprising ATO TCR-T against hepatocellular carcinoma (HCC), both vitro vivo. results lactate dehydrogenase cytokine assays demonstrated that enhanced cytotoxicity mediated AFP-specific promoted release IFN- γ vitro. Additionally, established HCC xenograft mouse model, combined low-dose exhibited heightened efficacy suppressing growth, no apparent adverse effects, comparable achieved through monotherapy. RNA-seq data unveiled significant activation ferroptosis-related pathway group comparison group. Mechanistically, synergy between augmented cells, while concurrently elevating intracellular mitochondrial levels ROS, expanding labile iron pool, impairing integrity membrane HepG2 cells. This multifaceted interaction culminated potentiation within tumor, primarily induced excess ROS. summary, co-administration vulnerability ferroptosis. susceptibility led inhibition growth stimulation anti-tumor response. These findings suggest repurposing atovaquone cell holds enhance treatment outcomes HCC.

Язык: Английский

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Gut-microbiota prompt activation of natural killer cell on alcoholic liver disease

Gut Microbes, Год журнала: 2023, Номер 15(2)

Опубликована: Ноя. 21, 2023

The liver is rich in innate immune cells, such as natural killer (NK) T and Kupffer cells associated with the gut microbiome. These are dysfunctional owing to alcohol consumption. However, there insufficient data on association between microbiome alcoholic disease (ALD). Therefore, purpose of this study was evaluate effects probiotic strains NK ALD patients. In total, 125 human blood samples [control (n = 22), hepatitis 43), cirrhosis 60]) were collected for flow cytometric analysis. C57BL/6J mice divided into four groups (normal, EtOH-fed, 2 EtOH+strain [Phocaeicola dorei Lactobacillus helveticus]). Lymphocytes isolated from mouse livers analyzed using cytometry. frequency increased patients decreased cirrhosis. expression NKp46, an cell-activating receptor, compared that control group. number cytotoxic CD56dimCD16+ significantly reduced We tested effect oral administration P. L. helveticus EtOH-fed mice. improved inflammation intestinal barrier damage caused by EtOH supply cell activity. these observations suggest may ameliorate regulating cells.

Язык: Английский

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Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 15, 2024

The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. treatment HCC has witnessed significant surge in recent years, with the emergence targeted immune therapy as an adjunct to early surgical resection. Adoptive cell (ACT) using tumor-infiltrating lymphocytes (TIL) shown promising results other types solid tumors. This article aims provide comprehensive overview intricate interactions between different TILs their impact on HCC, elucidate strategies for targeting neoantigens through TILs, address challenges encountered TIL therapies along potential solutions. Furthermore, this specifically examines oncogenic signaling pathways activation within tumor microenvironment infiltration dynamics TILs. Additionally, concise is provided regarding preparation techniques update clinical trials investigating TIL-based immunotherapy

Язык: Английский

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Exploiting the immune system in hepatic tumor targeting: Unleashing the potential of drugs, natural products, and nanoparticles

Pathology - Research and Practice, Год журнала: 2024, Номер 256, С. 155266 - 155266

Опубликована: Март 19, 2024

Язык: Английский

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Global research trends in the tumor microenvironment of hepatocellular carcinoma: insights based on bibliometric analysis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 1, 2024

This study aimed to use visual mapping and bibliometric analysis summarize valuable information on the tumor microenvironment (TME)-related research hepatocellular carcinoma (HCC) in past 20 years identify hotspots trends this field.

Язык: Английский

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Surgical treatment for hepatocellular carcinoma in era of multidisciplinary strategies

International Journal of Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Hepatocellular carcinoma (HCC) remains a significant global health challenge, with over 800,000 new cases diagnosed annually. This comprehensive review examines current surgical approaches and emerging multidisciplinary strategies in HCC treatment. While traditional criteria, such as the Barcelona Clinic Liver Cancer (BCLC) staging system, have been relatively conservative, recent evidence from high-volume Asian centers supports more aggressive carefully selected patients. The discusses evolution of selection including “Borderline Resectable HCC” classification which provides explicit guidance for decision-making. Technical innovations significantly enhanced precision, three-dimensional simulation, intraoperative navigation systems, advancement minimally invasive approaches. evaluates ongoing debate between anatomical versus non-anatomical resection role robotic surgery. In liver transplantation, expanded criteria beyond Milan show promising outcomes, while integration novel biomarkers imaging techniques improves patient selection. preoperative adjuvant therapies is increasingly important, trials demonstrating potential immune checkpoint inhibitors combined anti-VEGF agents both settings. Despite these advances, postoperative recurrence challenge. concludes that successful treatment requires personalized approach, integrating expertise technologies systemic considering individual factors regional variations practice patterns.

Язык: Английский

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Diverse approaches and sources to derive antitumor T cell for liver cancer: a single-cell sequence based research

Hepatology International, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Язык: Английский

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Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Hepatocellular carcinoma stands as one of the foremost contributors to cancer-associated fatalities globally, and limitations traditional treatment methods have prompted researchers explore new therapeutic options. Recently, cell therapy has emerged a promising approach for HCC, showing significant potential in improving patient outcomes. This review article explores use covering different types, mechanisms behind their effectiveness, recent advancements clinical trials, ongoing challenges. aims provide insightful perspectives future research applications treating HCC by synthesizing current knowledge.

Язык: Английский

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Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Апрель 17, 2024

Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard care advanced tumours, yet majority remain resistant to this therapy and urgent approaches needed boost efficacy these agents. Targeting liver endothelial cells, as orchestrators immune cell recruitment, within tumour microenvironment highly vascular cancer could potentially infiltration. We demonstrate successful culture primary human cells in organ-on-a-chip technology followed by perfusion peripheral blood mononuclear cells. confirm, confocal multiphoton imaging, capture adhesion response pro-inflammatory cytokines model. This multicellular platform sets foundation testing new therapies promoting leukocyte infiltration across endothelium well a model therapy, such chimeric antigen receptor (CAR)-T cell, migration endothelium.

Язык: Английский

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Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12630 - 12630

Опубликована: Авг. 10, 2023

Liver cancer is one of the most lethal malignant cancers worldwide. However, therapeutic options for advanced liver are limited and reveal scant efficacy. The current study investigated effects nivolumab (Niv) escitalopram oxalate (Esc) in combination on proliferation cells both vitro vivo. Significantly decreased viability HepG2 that were treated with Esc or Niv was observed a dose-dependent manner at 24 h, 48 72 h. Administration (50 μM) + (20 μM), (75 (5 over h exhibited synergistic effects, inhibiting survival cells. Additionally, treatment (1 Finally, survival. Com-pared controls, significantly increased sub-G1 portion annexin-V signals. In xenograft animal study, (6.66 mg/kg) (2.5 suppressed growth tumors nude mice. This reports first time combined administration cell proliferation, which may provide an alternative option treatment.

Язык: Английский

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