Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.

Background: Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.

Methods: We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.

Results: We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property.

Management and treatment of severe immune-related hepatotoxicity based on clinical and pathological characteristics.

Background: The management of severe immune-related hepatotoxicity (irH) needs to be further optimized. This study aims to analyze the clinical characteristics of severe irH; improve the therapeutic strategy, especially salvage treatment in steroid-refractory irH; and determine the safety of immune checkpoint inhibitor (ICPi)-rechallenge.

Methods: This multicenter retrospective study included patients who developed severe irH and those without irH after immunotherapy between May 2019 and June 2023.

Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma.

Background: The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.

Methods: From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.

Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer.

Background: Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.

Methods: This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022.

Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study.

Background: The role of conversion surgery in patients with unresectable biliary tract cancer who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery.

Methods: In this cohort study, patients with advanced biliary tract cancer who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively.

Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma.

Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field.

Lenvatinib combined with PD-1 inhibitor plus Gemox chemotherapy versus plus HAIC for advanced biliary tract cancer.

Objective: To compare the treatment efficacy and safety of lenvatinib and programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin plus gemcitabine (Gemox) chemotherapy or hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancer (BTC).

Method: This study involved 86 patients with advanced BTC receiving PD-1 inhibitor and lenvatinib combined with HAIC (P-L-H group) or Gemox chemothrapy (P-L-G group). Propensity score matching (PSM) (1:1) analysis was used to balance potential bias.

Single-cell RNA sequencing in cancer research: discovering novel biomarkers and therapeutic targets for immune checkpoint blockade.

Immune checkpoint blockade (ICB) has become a promising strategy in treating advanced cancers, providing significant survival benefits for patients with various cancer types. However, among the vast population of cancer patients, only a small fraction are able to respond to and derive benefits from ICB therapy. Numerous factors contribute to the diminished efficacy of ICB, with the complex tumor microenvironment (TME) playing an important role.

The efficacy and safety of bevacizumab as a salvage therapy for patients with advanced hepatocellular carcinoma targeting immune tolerance.

As is well understood that malignant tumour progression requires additional blood vessels to provide the nutrients necessary for growth. Many patients with advanced hepatocellular carcinoma (aHCC) experience disease progression after treatment with lenvatinib (Lenva) and immune checkpoint inhibitors (ICIs). Therefore, we designed a double-arm retrospective study to evaluate the antitumour activity of additional bevacizumab (Beva, an anti-vascular endothelial growth factor-targeting drug) as a means to reduce the blood vessels needed for tumour growth.

Radiation Therapy With Combination Therapy of Immune Checkpoint Inhibitors and Antiangiogenic Therapy for Hepatocellular Carcinoma.

Purpose: Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have limited efficacy in treating advanced hepatocellular carcinoma (HCC). The synergistic effect of systemic therapy and radiation therapy (RT) might resolve this problem. We aimed to investigate the effect of RT on the treatment outcomes of ICIs and antiangiogenic combination therapy in patients with advanced-stage HCC.

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study.

Background: A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world study.

Methods: Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers.

Development and validation of a selenium metabolism regulators associated prognostic model for hepatocellular carcinoma.

Background: Selenium metabolism has been implicated in human health. This study aimed to identify a selenium metabolism regulator-based prognostic signature for hepatocellular carcinoma (HCC) and validate the role of INMT in HCC.

Methods: Transcriptome sequencing data and clinical information related to selenium metabolism regulators in TCGA liver cancer dataset were analysed.

Prognostic value of SAT volume and density for predicting the outcome of patients with unresectable HCC treated with lenvatinib plus anti-PD-1 antibodies.

The combination of immunotherapy and lenvatinib has shown a good response for inoperable hepatocellular carcinoma (HCC) patients. However, a specific marker to predict the response, overall survival (OS) and progression-free survival (PFS) of this combination treatment is lacking. The present work focused on investigating whether subcutaneous adipose tissue (SAT) characteristics on CT could predict the response and survival for HCC patients who receive the combination treatment.

Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients.

Introduction: Combining lenvatinib with a programmed cell death protein-1 (PD-1) inhibitor has been explored for the treatment of un-resectable hepatocellular carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study failed to achieve the primary endpoints.

Methods: Patients with uHCC treated with lenvatinib and PD-1 inhibitors were included.

Development and validation of a genomic instability-related lncRNA prognostic model for hepatocellular carcinoma.

Genomic instability is a characteristic of tumors, and recent studies have shown that it is related to a poor prognosis of multiple cancers. Long non-coding RNAs (lncRNAs) have become a research hotspot in recent years, and many unknown biological functions are being explored. For example, some lncRNAs play a critical role in the initiation and progression of multiple cancer types by modulating genomic instability.

Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma.

Background: Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear.

Objective: The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib.

Differentially expressed liver exosome-related genes as candidate prognostic biomarkers for hepatocellular carcinoma.

Background: Exosomes are involved in cell-to-cell communication, neovascularization, cancer metastasis, and drug resistance, which all play an important role in the occurrence and progression of hepatocellular carcinoma (HCC). Because there are few mechanistic studies about the function of exosomes in HCC, the goals of this study were to identify exosome-related genes in HCC, to establish a reliable prognostic model for HCC, and to explore underlying mechanisms.

Methods: The exoRBase and The Cancer Genome Atlas (TCGA) databases were used to analyze differentially expressed genes (DEGs).

Identification of an m6A-Related Long Noncoding RNA Risk Model for Predicting Prognosis and Directing Treatments in Patients With Colon Adenocarcinoma.

N6-methyladenosine (m6A) and lncRNAs have been implicated in the development of colon cancer, including tumorigenesis, migration, and invasion. However, the specific effect of m6A regulators on lncRNAs is not clear, and m6A-related lncRNAs may be new prognostic biomarkers and may help direct treatment and medication. We identified 29 prognostic m6A-related lncRNAs and constructed a risk model using 12 lncRNAs.