Deciphering the Multifaceted Immune Landscape of Unresectable Primary Liver Cancer to Predict Immunotherapy Response.

Immunotherapies employing PD-1/PD-L1 immune checkpoint inhibitors (ICIs) are vital for primary liver cancer (PLC), but response rates remain unsatisfying. Accurate differentiation of responders from non-responders to immunotherapy is imperative. Here, single-cell-scaled mass cytometry analysis on sequential peripheral blood mononuclear cells (PBMCs) from ICI-treated PLC patients is conducted, and tissue residence of immune subpopulations is assessed via multiplex immunohistochemistry.

Hyperactivation of β-catenin signal in hepatocellular carcinoma recruits myeloid-derived suppressor cells through PF4-CXCR3 axis.

The high mutation rate of CTNNB1 (37 %) and Wnt-β-catenin signal-associated genes (54 %) has been notified in hepatocellular carcinoma (HCC). The activation of Wnt-β-catenin signal pathway was reported to be associated with an immune "desert" phenotype, but the underlying mechanism remains unclear. Here we mainly employed orthotopic HCC models to explore on it.

Integrated characterization of hepatobiliary tumor organoids provides a potential landscape of pharmacogenomic interactions.

Despite considerable efforts to identify human liver cancer genomic alterations that might unveil druggable targets, the systematic translation of multiomics data remains challenging. Here, we report success in long-term culture of 64 patient-derived hepatobiliary tumor organoids (PDHOs) from a Chinese population. A divergent response to 265 metabolism- and epigenetics-related chemicals and 36 anti-cancer drugs is observed.

A Noninvasive Approach to Evaluate Tumor Immune Microenvironment and Predict Outcomes in Hepatocellular Carcinoma.

Unlabelled: It is widely recognized that tumor immune microenvironment (TIME) plays a crucial role in tumor progression, metastasis, and therapeutic response. Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis, there are still lack of effective radiomic-based model to evaluate TIME status, let alone predict clinical outcome and immune checkpoint inhibitor (ICIs) response for hepatocellular carcinoma (HCC). In this study, we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.

Detection of Putative Mutation I873S in the Sodium Channel of (Bagnall) Which May Be Associated with Pyrethroid Resistance.

Pyrethroid resistance of thrips has been reported in many countries, and knockdown resistance () has been identified as a main mechanism against pyrethroids in many insects. To characterize pyrethroid resistance in from the Hainan Province of China, we conducted a biological assay and sequenced the voltage-gated sodium channel gene domain II from field populations. It showed high resistance to the pyrethroids for 2019 and 2020, in which LC to lambda-cyhalothrin of was 1683.

Integrated Multi-Omics Landscape of Liver Metastases.

Background & Aims: Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs.

Methods: Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort.

Single-cell atlas of diverse immune populations in the advanced biliary tract cancer microenvironment.

Immunotherapies have been explored in treating solid tumors, albeit with disparate clinical effects in distinct cancer types. Systematic interrogation of immune cells in the tumor microenvironment (TME) is vital to the prediction of immunotherapy response and the development of innovative immunotherapeutics. To comprehensively characterize the immune microenvironment in advanced biliary tract cancer (BTC), we utilized single-cell RNA sequencing in unselected viable cells from 16 matched samples, and identified nineteen cell subsets from a total of 45,851 cells, in which exhausted CD8 T cells, macrophages, and dendritic cells (DCs) in BTC were shown to augment and communicate within the TME.

Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors.

Neoantigen-directed therapy lacks preclinical models recapitulating neoantigen characteristics of original tumors. It is urgent to develop a platform to assess T cell response for neoantigen screening. Here, immunogenic potential of neoantigen-peptides of tumor tissues and matched organoids (n = 27 pairs) are analyzed by Score tools with whole genome sequencing (WGS)-based human leukocyte antigen (HLA)-class-I algorithms.

Comprehensive analysis of spatial architecture in primary liver cancer.

Heterogeneity is the major challenge for cancer prevention and therapy. Here, we first constructed high-resolution spatial transcriptomes of primary liver cancers (PLCs) containing 84,823 spots within 21 tissues from seven patients. The progressive comparison of spatial tumor microenvironment (TME) characteristics from nontumor to leading-edge to tumor regions revealed that the tumor capsule potentially affects intratumor spatial cluster continuity, transcriptome diversity, and immune cell infiltration.

The Wnt/β-catenin signaling pathway in the tumor microenvironment of hepatocellular carcinoma.

The Wnt/β-catenin signaling pathway regulates many aspects of tumor biology, and many studies have focused on the role of this signaling pathway in tumor cells. However, it is now clear that tumor development and metastasis depend on the two-way interaction between cancer cells and their environment, thereby forming a tumor microenvironment (TME). In this review, we discuss how Wnt/β-catenin signaling regulates cross-interactions among different components of the TME, including immune cells, stem cells, tumor vasculature, and noncellular components of the TME in hepatocellular carcinoma.

The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice.

Background & Aims: Preoperative obstructive jaundice is usually associated with higher post-operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota.

Discovery of a Carbamoyl Phosphate Synthetase 1-Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis.

Background And Aims: Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in-depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)-deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as a target for HCC prevention.

MA Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma.

N-methyladenosine (mA) has been reported as an important mechanism of posttranscriptional regulation. Programmed death-ligand 1 (PD-L1) is a primary immune inhibitory molecule expressed on tumor cells that promotes immune evasion. Here we report ALKBH5 as an important mA demethylase that orchestrates PD-L1 expression in intrahepatic cholangiocarcinoma (ICC).

Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.

Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs.

The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma.

Immunotherapy is a powerful therapeutic strategy for end-stage hepatocellular carcinoma (HCC). It is well known that T cells, including CD8+PD-1+ T cells, play important roles involving tumor development. However, their underlying phenotypic and functional differences of T cell subsets remain unclear.

Trajectory and Functional Analysis of PD-1 CD4CD8 T Cells in Hepatocellular Carcinoma by Single-Cell Cytometry and Transcriptome Sequencing.

The spatial heterogeneity of immune microenvironment in hepatocellular carcinoma (HCC) remains elusive. Here, a single-cell study involving 17 432 600 immune cells of 39 matched HCC (T), nontumor (N), and leading-edge (L) specimens by mass cytometry is conducted. The tumor-associated CD4/CD8 double-positive T (DPT) cells are found enriched in L regions with synergetic expression of PD-1/HLA-DR/ICOS/CD45RO and exhibit a higher level of IFN-, TNF-, and PD-1 upon stimulation.

Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways.

Aim: To investigate the effects of piperlongumine (PL), an anticancer alkaloid from long pepper plants, on the primary myeloid leukemia cells from patients and the mechanisms of action.

Methods: Human BM samples were obtained from 9 patients with acute or chronic myeloid leukemias and 2 patients with myelodysplastic syndrome (MDS). Bone marrow mononuclear cells (BMMNCs) were isolated and cultured.