M2-like tumor-associated macrophage-secreted CCL2 facilitates gallbladder cancer stemness and metastasis.

Background: The predominant immune cells in solid tumors are M2-like tumor-associated macrophages (M2-like TAMs), which significantly impact the promotion of epithelial-mesenchymal transition (EMT) in tumors, enhancing stemness and facilitating tumor invasion and metastasis. However, the contribution of M2-like TAMs to tumor progression in gallbladder cancer (GBC) is partially known.

Methods: Immunohistochemistry was used to evaluate the expression of M2-like TAMs and cancer stem cell (CSC) markers in 24 pairs of GBC and adjacent noncancerous tissues from patients with GBC.

YTHDF3-mediated m6A modification of NKD1 regulates hepatocellular carcinoma invasion and metastasis by activating the WNT/β-catenin signaling axis.

N6-methyladenosine (m6A) alteration is an epigenetic regulator widely involved in the tumorigenicity of hepatocellular carcinoma (HCC). The role of YTH N6-methyladenosine RNA binding protein F3 (YTHDF3), an m6A reader in HCC, requires further investigation. Here, we aim to explore the biological properties of YTHDF3 in HCC and its potential mechanisms.

LAIR1 promotes hepatocellular carcinoma cell metastasis and induces M2-macrophage infiltration through activating AKT-IKKβ-p65 axis.

LAIR1, a receptor found on immune cells, is capable of binding to collagen and is involved in immune-related diseases. However, the precise contribution of LAIR1 expressed on hepatocellular carcinoma (HCC) cells to tumor microenvironment is still unclear. In our study, bioinformatics analysis and immunofluorescence were employed to study the correlation between LAIR1 levels and clinical indicators.

Hypoxia-responsive lncRNA MIR155HG promotes PD-L1 expression in hepatocellular carcinoma cells by enhancing HIF-1α mRNA stability.

The microenvironment of hepatocellular carcinoma (HCC) is characterized by hypoxia, which leads to immune evasion of HCC. Therefore, gaining a comprehensive understanding of the mechanism underlying the impact of hypoxia on HCC cells may provide valuable insights into immune checkpoint therapy. Based on analysis of databases and clinical samples, we observed that expression level of programmed cell death ligand 1 (PD-L1) and long non-coding RNA (lncRNA) MIR155HG in patients in the hypoxia group were higher than those in the non-hypoxia group.

LAIR1-mediated resistance of hepatocellular carcinoma cells to T cells through a GSK-3β/β-catenin/MYC/PD-L1 pathway.

Background: An increasing number of studies have reported the involvement of oncogenes in the regulation of the immune system. LAIR1 is an immunosuppressive molecule and its role in immune-related diseases has been mainly reported. To date, it is unclear whether LAIR1 in tumor cells is involved in immune regulation.

SUMOylation inhibitors activate anti-tumor immunity by reshaping the immune microenvironment in a preclinical model of hepatocellular carcinoma.

Purpose: High levels of heterogeneity and immunosuppression characterize the HCC immune microenvironment (TME). Unfortunately, the majority of hepatocellular carcinoma (HCC) patients do not benefit from immune checkpoint inhibitors (ICIs) therapy. New small molecule therapies for the treatment of HCC are the goal of our research.

Single-cell atlas reveals characteristic changes in intrahepatic HBV-specific leukocytes.

Hepatitis B virus (HBV)-specific CD8 T cells play a central role in the clearance of virus and HBV-related liver injury. Acute infection with HBV induces a vigorous, multifunctional CD8 T cell response, whereas chronic one exhibits a weaker response. Our study elucidated HBV-specific T cell responses in terms of viral abundance rather than the timing of infection.

Unpacking the complexity of nuclear IL-33 (nIL-33): a crucial regulator of transcription and signal transduction.

Interleukin-33 (IL-33) (NF-HEV), a chromatin-associated nuclear cytokine, is a member of the IL-1 family. IL-33 possesses a nuclear localization signal and a homeodomain (a structure resembling a helix-turn-helix) that can bind to nuclear chromatin. Research has revealed that IL-33 can function as a nuclear factor to regulate various biological processes.

A modified immune cell infiltration score achieves ideal stratification for CD8 T cell efficacy and immunotherapy benefit in hepatocellular carcinoma.

Immunotherapy, which aims to enhance the function of T cells, has emerged as a novel therapeutic approach for hepatocellular carcinoma (HCC). Nevertheless, the clinical utility of using flow cytometry to assess immune cell infiltration (ICI) is hindered by its cumbersome procedures, prompting the need for more accessible methods. Here, we acquired gene expression profiles and survival data of HCC from TCGA and GSE10186 datasets.

TGF-β-p-STAT1-LAIR2 axis has a "self-rescue" role for exhausted CD8 T cells in hepatocellular carcinoma.

Background: TGF-β is related to the function of T cells in the tumor microenvironment. However, the characteristics of TGF-β affecting the function of CD8 T cells in hepatocellular carcinoma (HCC) have not been clearly resolved.

Methods: In this study, flow cytometry, mass cytometry, immunohistochemistry, RNA-seq, single-cell RNA-seq, assay for transposase-accessible chromatin with high throughput sequencing, chromatin immunoprecipitation, and dual-luciferase reporter gene assay were used to study the regulatory effect and molecular mechanism of TGF-β on HCC infiltrating CD8 T cells.

IL-33/ST2 antagonizes STING signal transduction via autophagy in response to acetaminophen-mediated toxicological immunity.

Background: Interleukin-33 (IL-33), defined as "alarming", exert diverse functions through signaling via the suppression of tumorigenicity 2 (ST2). However, the physiological roles of IL-33/ST2 signaling during acetaminophen (APAP)-induced liver injury are still poorly understood by modern medicine (AILI). This research aims to explore the relationship between IL-33/ST2 and stimulator of interferon (IFN) response cGAMP interactor 1 (STING)-mediated signal transduction.

SUMOylated IL-33 in the nucleus stabilizes the transcription factor IRF1 in hepatocellular carcinoma cells to promote immune escape.

Interleukin-33 (IL-33) functions both as a secreted cytokine and as a nuclear factor, with pleiotropic roles in cancer and immunity. Here, we explored its role in hepatocellular carcinoma (HCC) and identified that a posttranslational modification altered its nuclear activity and promoted immune escape for HCC. IL-33 abundance was overall decreased but more frequently localized to the nucleus in patient HCC tissues than in normal liver tissues.

XPO1 intensifies sorafenib resistance by stabilizing acetylation of NPM1 and enhancing epithelial-mesenchymal transition in hepatocellular carcinoma.

Emerging studies have suggested that exportin-1 (XPO1) plays a pivotal role in hepatocellular carcinoma (HCC). However, the underlying mechanism of XPO1 in HCC sorafenib resistance remains enigmatic. The expression of XPO1 in HCC tumor tissues and sorafenib-resistant (SR) cells were analyzed by bioinformatics analysis, immunohistochemistry (IHC) and Western blotting.

Targeted inhibition of RBPJ transcription complex alleviates the exhaustion of CD8 T cells in hepatocellular carcinoma.

Impaired function of CD8 T cells in hepatocellular carcinoma (HCC) is an important reason for acquired resistance. Compared with single-target inhibitors, small-molecule compounds that could both inhibit tumor cells and alleviate T cell exhaustion are more promising to reduce resistance. In this study, we screened immunosuppressive targets in HCC by combining cancer-immunity cycle score with weighted gene co-expression network and system analysis.

Prognostic and immunotherapeutic predictive value of interleukin enhancer-binding factor 3 in hepatocellular carcinoma: Integrated bioinformatics and experimental analysis.

Interleukin enhancer-binding factor 3 (ILF3) as an RNA-binding protein that plays a critical role in the process of cancer and antiviral responses. However, no researcher has focused on the pan-cancer analysis of ILF3, and the effect of ILF3 on tumor immunity is still largely unclear. This study synthetically analyzed the relationship between the expression of ILF3 across various cancers and prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), tumor immune cell infiltration, and common immune checkpoint molecules by multiple bioinformatics databases.

Lipopolysaccharide facilitates immune escape of hepatocellular carcinoma cells via m6A modification of lncRNA MIR155HG to upregulate PD-L1 expression.

Recent studies have suggested that the initiation and progression of hepatocellular carcinoma (HCC) are closely associated with lipopolysaccharide (LPS) of intestinal bacteria. However, the role of LPS in immune regulation of HCC remains largely unknown. An orthotopic Hepa1-6 tumor model of HCC was constructed to analyze the effect of LPS on the expression of immune checkpoint molecules PD-1 and PD-L1.

lncRNA MIAT targets miR-411-5p/STAT3/PD-L1 axis mediating hepatocellular carcinoma immune response.

Emerging evidences have shown that long noncoding RNA (lncRNA) plays an important role in the immune escape of cancer cells. Our previous study has demonstrated that lncRNA MIAT is associated with the immune infiltration of hepatocellular carcinoma (HCC). However, the underlying mechanism of MIAT regulating the PD-L1-mediated immune escape of HCC is poorly understood.

Increased effects of 2,5-dimethylcelecoxib on sensitivity of hepatocellular carcinoma cells to sorafenib via CYP3A5 expression and activation of AMPK.

As the occurrence and development of HCC are often accompanied by inflammation, the combination of sorafenib with other therapeutic drugs, especially anti-inflammatory drugs, is one of the directions to be explored at present. Our previous research has been focused on the anti-inflammatory drug 2,5-dimethylcelecoxib (DMC), whether DMC combined with sorafenib could elevate the effect of inhibiting HCC deserves further exploration. In this study, we found that DMC induced CYP3A5 expression in HCC cells in a time-dependent and concentration dependent manner.

Engineering 'Enzymelink' for screening lead compounds to inhibit mPGES-1 while maintaining prostacyclin synthase activity.

This study investigated our Enzymelinks, COX-2-10aa-mPGES-1 and COX-2-10aa-PGIS, as cellular cross-screening targets for quick identification of lead compounds to inhibit inflammatory PGE biosynthesis while maintaining prostacyclin synthesis. We integrated virtual and wet cross-screening using Enzymelinks to rapidly identify lead compounds from a large compound library. From 380,000 compounds virtually cross-screened with the Enzymelinks, 1576 compounds were identified and used for wet cross-screening using HEK293 cells that overexpressed individual Enzymelinks as targets.

Interleukin 33 mediates hepatocyte autophagy and innate immune response in the early phase of acetaminophen-induced acute liver injury.

Despite interleukin 33 (IL-33) functions as an "alarmin" released from hepatic dead cells in response to tissue damages, the interrelationship between IL-33-mediated hepatocyte autophagy and innate immune response in the acetaminophen (APAP)-induced liver injury (AILI) process remains obscure. This study aimed to explore the regulation of IL-33 on hepatocyte autophagy and macrophage polarization after APAP challenge in vivo and vitro. We found IL-33 released from hepatic necrosis was elevated in the AILI mouse model.