Multi-model analysis of gallbladder cancer reveals the role of OxLDL-absorbing neutrophils in promoting liver invasion.

Background: Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading.

Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI).

Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients).

Spatial immunophenotypes predict clinical outcome in intrahepatic cholangiocarcinoma.

Background & Aims: Intrahepatic cholangiocarcinoma (iCCA) is a severe malignant tumour that shows only modest responses to immunotherapy. We aimed to identify the spatial immunophenotypes of iCCA and delineate potential immune escape mechanisms.

Method: Multiplex immunohistochemistry (mIHC) was performed to quantitatively evaluate the distribution of 16 immune cell subsets in intratumour, invasive margin and peritumour areas in a cohort of 192 treatment-naïve patients with iCCA.

Elevated Mast Cell Abundance Is Associated with Enrichment of CCR2+ Cytotoxic T Cells and Favorable Prognosis in Lung Adenocarcinoma.

Unlabelled: Mast cells constitute indispensable immunoregulatory sentinel cells in the tumor microenvironment. A better understanding of the regulation and functions of mast cells in lung adenocarcinoma (LUAD) could uncover therapeutic approaches to reprogram the immunosuppressive tumor microenvironment. Here, we performed flow cytometry and single-cell RNA sequencing (scRNA-seq) of patient LUAD samples to comprehensively characterize LUAD-infiltrating mast cells.

Single-cell profiling reveals mechanisms of uncontrolled inflammation and glycolysis in decidual stromal cell subtypes in recurrent miscarriage.

Study Question: Do distinct subpopulations of decidual stromal cells (DSCs) exist and if so, are given subpopulations enriched in recurrent miscarriage (RM)?

Summary Answer: Three subpopulations of DSCs were identified from which inflammatory DSCs (iDSCs) and glycolytic DSCs (glyDSCs) are significantly enriched in RM, with implicated roles in driving decidual inflammation and immune dysregulation.

What Is Known Already: DSCs play crucial roles in establishing and maintaining a successful pregnancy; dysfunction of DSCs has been considered as one of the key reasons for the development of RM.

Study Design, Size, Duration: We collected 15 early decidual samples from five healthy donors (HDs) and ten RM patients to perform single-cell RNA sequencing (scRNA-seq).

Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications.

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5 DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease and high mortality. The aetiology and pathogenesis of MDA5 DM are still largely unknown. Here we describe the immune signatures of MDA5 DM via single-cell RNA sequencing, flow cytometry and multiplex immunohistochemistry in peripheral B and T cells and in affected lung tissue samples from one patient.

Multi-omics characterization reveals the pathogenesis of liver focal nodular hyperplasia.

The molecular landscape and pathogenesis of focal nodular hyperplasia (FNH) have yet to be elucidated. We performed multi-omics approaches on FNH and paired normal liver tissues from 22 patients, followed by multi-level bioinformatic analyses and experimental validations. Generally, FNH had low mutation burden with low variant allele frequencies, and the mutation frequency significantly correlated with proliferation rate.

Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities.

Background: Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.

Methods: We performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues.

Geospatial Immune Heterogeneity Reflects the Diverse Tumor-Immune Interactions in Intrahepatic Cholangiocarcinoma.

Unlabelled: Intrahepatic cholangiocarcinoma (iCCA) exhibits extensive intratumoral heterogeneity and an extremely high mortality rate. Here, we performed whole-exome sequencing, RNA sequencing, T-cell receptor (TCR) sequencing, and multiplexed immunofluorescence on 207 tumor regions from 45 patients with iCCA. Over half of iCCA displayed intratumoral heterogeneity of immune infiltration, and iCCA were classified into sparsely, heterogeneously, and highly infiltrated subgroups with distinct immunogenomic characteristics.

Two Distinct Immune Cell Signatures Predict the Clinical Outcomes in Patients With Amyopathic Dermatomyositis With Interstitial Lung Disease.

Objective: Amyopathic dermatomyositis (ADM) is a heterogeneous and life-threatening autoimmune disease with a high mortality rate. In particular, anti-melanoma differentiation-associated protein 5 antibody-positive patients are at a high risk of developing rapidly progressive interstitial lung disease (RPILD). This study was undertaken to identify immunologic signatures among patients who have ADM with ILD (ADM-ILD) and to discover the biomarkers predicting prognosis.

Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCA) and peripheral small duct type (iCCA). S100P + SPP1- iCCA has significantly reduced levels of infiltrating CD4 T cells, CD56 NK cells, and increased CCL18 macrophages and PD1CD8 T cells compared to S100P-SPP1 + iCCA.

Distribution and density of tertiary lymphoid structures predict clinical outcome in intrahepatic cholangiocarcinoma.

Background & Aims: The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TLSs in iCCA.

Methods: We retrospectively included 962 patients from 3 cancer centers across China.

Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level.

Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA sequencing and spatial transcriptomics. Strikingly, the metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as M2-like macrophages.

Global immune characterization of HBV/HCV-related hepatocellular carcinoma identifies macrophage and T-cell subsets associated with disease progression.

Diverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions.

PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome.

Objective: Immunotherapy targeting the programmed cell death protein-1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) pathway has been observed to be efficient in several solid tumors. We aim to investigate the prognostic significance of PD-1/PD-L1 expression profile in intrahepatic cholangiocarcinoma (ICC).

Materials And Methods: We investigated the expression of PD-1, PD-L1, CD8 T cells, and CD68 macrophages in paired tumor and adjacent normal tissues from 322 ICC patients using tyramide signal amplification (TSA)-based multiplexed immunohistochemistry.

The distribution of immune cells within combined hepatocellular carcinoma and cholangiocarcinoma predicts clinical outcome.

Background: This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-ICC).

Patients And Methods: The density of tumor-infiltrating CD3 , CD8 , CD163 , and Foxp3 immune cells, as well as Programmed cell death 1, Programmed cell death-ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC-ICC by immunohistochemistry. The immune index was established to stratify patients.

PD1 CD8 T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

Background: CD8 T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking.

Methods: We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (n = 358 and n = 254), who underwent surgical resection.

Highly immunosuppressive HLADR regulatory T cells are associated with unfavorable outcomes in cervical squamous cell carcinoma.

Regulatory T cells (Tregs) are crucial for the maintenance of peripheral tolerance, but they also limit beneficial responses through cancer-induced immunoediting. The roles of Treg subsets in cervical squamous cell carcinoma (CSCC) are currently unknown. Here, we aimed to perform an extensive study with an increased resolution of the Treg compartment in the peripheral blood and tumor tissues of CSCC patients.

CD4T Cell Subset Profiling in Biliary Atresia Reveals ICOS Regulatory T Cells as a Favorable Prognostic Factor.

Biliary atresia (BA) is a destructive pediatric liver disease and CD4T cell activation is demonstrated to play an important role in BA. However, a comprehensive scenario regarding the involvement of CD4T cell subsets to the development of BA remains unclear. Here, we aim to explore the infiltration of CD4T cell subsets and their clinical significance in BA.

Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma.

As a major cellular component in tumor microenvironment, the distribution, frequency, and prognostic significance of infiltrating B cell subsets in hepatocellular carcinoma (HCC) remain controversial. Using tyramide signal amplification (TSA) based fluorescent multiplexed immunohistochemistry , we evaluated the distribution and frequency of B cell subsets in two independent HCC cohorts (n = 619). The results were further confirmed by flow cytometry.