Effective Antiviral Therapy Improves Immunosuppressive Activities in the Immune Microenvironment of Hepatocellular Carcinoma by Alleviating Inflammation and Fibrosis.

Background And Aims: The immune microenvironment (IME) plays a crucial role in the progression of hepatocellular carcinoma (HCC). In HCC, the IME is often compromised by hepatitis B virus (HBV) infection, chronic inflammation, and fibrosis. Both antiviral therapy (AVT) and the alleviation of inflammation and fibrosis (AIF) have been shown to improve prognosis.

Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma.

Background & Aims: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA.

Methods: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy.

Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma.

Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples.

Enhancing hepatocellular carcinoma management: prognostic value of integrated CCL17, CCR4, CD73, and HHLA2 expression analysis.

Purpose: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC.

Peripheral Lymphocytes in Primary Liver Cancers: Elevated NK and CD8+ T Cells and Dysregulated Selenium Metabolism.

Peripheral blood lymphocytes (PBLs), which play a pivotal role in orchestrating the immune system, garner minimal attention in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The impact of primary liver cancers on PBLs remains unexplored. In this study, flow cytometry facilitated the quantification of cell populations, while transcriptome of PBLs was executed utilizing 10× single-cell sequencing technology.

MAIT cells confer resistance to Lenvatinib plus anti-PD1 antibodies in hepatocellular carcinoma through TNF-TNFRSF1B pathway.

The combination of antiangiogenic agents and immune checkpoint inhibitors is more efficient than monotherapy in the management of hepatocellular carcinoma (HCC). Lenvatinib plus anti-PD1 antibodies have become the mainstay in HCC treatment. However, more than half the patients with HCC are non-responsive, and the mechanisms underlying drug resistance are unknown.

Lenvatinib Induces Immunogenic Cell Death and Triggers Toll-Like Receptor-3/4 Ligands in Hepatocellular Carcinoma.

Purpose: Immunogenic cell death (ICD) is a cell death modality that plays a vital role in anticancer therapy. In this study, we investigated whether lenvatinib induces ICD in hepatocellular carcinoma and how it affects cancer cell behavior.

Patients And Methods: Hepatoma cells were treated with 0.

Integrative analyses identify CD73 as a prognostic biomarker and immunotherapeutic target in intrahepatic cholangiocarcinoma.

Background: CD73 promotes progression in several malignancies and is considered as a novel immune checkpoint. However, the function of CD73 in intrahepatic cholangiocarcinoma (ICC) remains uncertain. In this study, we aim to investigate the role of CD73 in ICC.

Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: A retrospective study.

Purpose: We aimed to investigate the feasibility of lenvatinib plus anti-PD-1 therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC).

Methods: Patients with initially unresectable HCC who received combined lenvatinib and anti-PD-1 antibody between May 2020 and Jan 2022 in Zhongshan Hospital were retrospectively analyzed. Tumor response and resectability were assessed by imaging every two months according to RECIST version 1.

The LINC00152/miR-205-5p/CXCL11 axis in hepatocellular carcinoma cancer-associated fibroblasts affects cancer cell phenotypes and tumor growth.

Background: CXCL11 has been reported to be up-regulated in hepatocellular carcinoma (HCC) tissues and cancer-associated fibroblasts (CAFs), and CAF-secreted CXCL11 has been found to promote HCC cell proliferation and migration. Knowledge on how CAFs promote HCC progression is imperative for the future design of anti-tumor drugs addressing the high rates of disease recurrence. Herein, we propose a mechanism by which LINC00152 positively regulates CXCL11 expression and, subsequently, HCC cell phenotypes and growth characteristics via miR-205-5p in CAFs.

Deep-learning-based analysis of preoperative MRI predicts microvascular invasion and outcome in hepatocellular carcinoma.

Background: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC.

Methods: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status.

Dissecting Intra-Tumoral Changes Following Immune Checkpoint Blockades in Intrahepatic Cholangiocarcinoma Single-Cell Analysis.

Purpose: To dissect the tumor ecosystem following immune checkpoint blockades (ICBs) in intrahepatic cholangiocarcinoma (ICC) at a single-cell level.

Methods: Single-cell RNA sequencing (scRNA-seq) data of 10 ICC patients for the ICB clinical trial were extracted from GSE125449 and systematically reanalyzed. Bulk RNA-seq data of 255 ICC patients were analyzed.

Antiviral therapy improves postoperative survival of patients with HBV-related hepatocellular carcinoma.

Background: We aimed to investigate whether improvements in the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who have undergone hepatectomy are associated with reductions in the liver inflammation and fibrosis by antiviral therapy (AVT).

Methods: Patients who underwent hepatectomy and re-hepatectomy for HBV-related HCC between 2010 and 2019 were divided into two groups. Histological changes in liver were compared between initial and recurrence stages within each group.

BRG1 regulates lipid metabolism in hepatocellular carcinoma through the PIK3AP1/PI3K/AKT pathway by mediating GLMP expression.

Background: Brahma-related gene 1 (BRG1) is essential for embryogenesis and cellular metabolism. A deficiency of BRG1 in vivo decreases lipid droplets, but the molecular mechanism underlying its role in lipid metabolism associated with hepatocellular carcinoma (HCC) remains unknown.

Aims: We aimed to determine the role of BRG1 in lipid metabolism in HCC.

Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis.

Cancer-associated fibroblasts (CAFs) are commonly acquired activated extracellular matrix (ECM)-producing myofibroblasts, a phenotypes with multiple roles in hepatic fibrogenesis and carcinogenesis via crosstalk with cohabitating stromal/cancer cells. Here, we discovered a mechanism whereby CAF-derived cytokines enhance hepatocellular carcinoma (HCC) progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells. CAFs secreted significantly higher levels of CXCL11 than normal fibroblasts (NFs), and CXCL11 also had comparatively higher expressions in HCC tissues, particularly in metastatic tissues, than para-carcinoma tissues.

MNS1 promotes hepatocarcinogenesis and metastasis via activating PI3K/AKT by translocating β-catenin and predicts poor prognosis.

Background & Aims: Hepatocellular carcinoma (HCC) is a fatal disease characterized by vast molecular heterogeneity. Although major advances in tumour genetics has led to the identification of new biomarkers, the prognosis of patients with HCC remains dismal.

Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to evaluate meiosis-specific nuclear structural 1 (MNS1) expression in HCC cells.

Clinical significance of herpes virus entry mediator expression in hepatitis B virus-related hepatocellular carcinoma.

Herpes virus entry mediator (HVEM) is overexpressed in several malignancies, including hepatocellular carcinoma (HCC). However, to the best of our knowledge, the clinical significance of HVEM in hepatitis B virus (HBV)-related HCC remains unclear. Thus, the present study aimed to explore the clinical significance of HVEM in HBV-related HCC.

Hepatic stellate cells promote the progression of hepatocellular carcinoma through microRNA-1246-RORα-Wnt/β-Catenin axis.

Hepatic stellate cells (HSCs) play vital roles in tumorigenesis and progression of hepatocellular carcinoma (HCC). However, there remains a lack of high-throughput studies on gene expression alterations in HCC cells in response to direct interactions with HSCs. In this study, we established a direct co-culture model of HSCs and HCC cells.

ROR-α-1 inhibits the proliferation, invasion, and migration of hepatocellular carcinoma MHCC97H via downregulation of chemokine CXCL5.

Hepatocarcinogenesis is a complicated process that is affected by a variety of microenvironmental factors, such as secretory chemokines and cell-extracellular matrix (ECM). Retinoic acid receptor-related orphan receptor (ROR)-α has been shown to attenuate tumor invasiveness by inducing suppressive cell microenvironment, and its low expression was associated with a worse prognosis in HCC patients. In the present study, we attempted to investigate the role and mechanism of the dominant transcript of ROR-α, ROR-α-1, in HCC development and progression.

Daily decrease of post-operative alpha-fetoprotein by 9% discriminates prognosis of HCC: A multicenter retrospective study.

Background: Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy.

Results: Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.