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Updated: Dec 13, 2025

Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary
Jin Sung Jang1,2, Brian D Juran3, Kevin Y Cunningham4,5
1Medical Genome Facility, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Insights
Primary biliary cholangitis (PBC) alters peripheral immune cells. This study used mass cytometry to identify specific changes in T cells, B cells, and monocytes in PBC patients, offering insights into disease progression.
Area of Science:
- Immunology
- Hepatology
- Autoimmune Diseases
Background:
- Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease.
- The precise relationship between PBC and the peripheral immune system is not fully understood.
- Peripheral immune system dysregulation may play a role in PBC pathogenesis and progression.
Purpose of the Study:
- To conduct the first mass cytometry (CyTOF)-based immunophenotyping analysis of the peripheral immune system in PBC patients at single-cell resolution.
- To identify specific immune cell types and subsets associated with PBC.
- To explore differences in immune cell profiles between PBC patients with and without cirrhosis.
Main Methods:
- Mass cytometry (CyTOF) was performed on peripheral blood mononuclear cells (PBMCs) from 33 PBC patients and 33 healthy controls.
- Hierarchical clustering was used to analyze immune cell abundance and marker expression.
- Statistical methods identified significant differences in immune cell subsets between groups.
Main Results:
- Lower abundance of gamma-delta T cells, specific CD8+ T cells, and memory B cells were observed in PBC patients compared to controls.
- Higher abundance of monocytes and naive B cells were found in PBC patients.
- Specific naive B cell subsets were elevated in cirrhotic PBC patients, while memory B cell subsets were decreased.
Conclusions:
- Peripheral immune system alterations, particularly in T and B cell subsets, are associated with PBC.
- Distinct immune cell profiles correlate with disease stage (cirrhosis) in PBC.
- Further immunophenotyping research may reveal novel biomarkers and therapeutic targets for PBC.
Abstract:
The relationship between primary biliary cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n = 33) and age-/sex-matched healthy controls (n = 33) to obtain immune cell abundance and marker expression profiles. Hierarchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+ T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3-CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3-CD19+CD20+CD24-CD27-) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

