# Systemic immune classification related to immune exhaustion evaluates the clinical response of patients with HBV-HCC after transarterial chemoembolization

## TL;DR

This study uses immune classification to predict how patients with liver cancer respond to a specific treatment, helping identify those who may benefit most from further immunotherapy.

## Contribution

The study introduces a systemic immune classification (SIC) method to evaluate clinical responses in HBV-related hepatocellular carcinoma patients after TACE treatment.

## Key findings

- HBV-HCC patients were classified into three immune subtypes using immune exhaustion phenotypes and proteins.
- Cluster 3 was linked to poor prognosis and higher immune checkpoint expression.
- The SIC method achieved high accuracy in predicting patient survival with area under the curve exceeding 0.8.

## Abstract

Transarterial chemoembolization (TACE) has the potential to activate the immune system and regulate the tumor microenvironment. This study assesses the clinical response of patients with HBV-related hepatocellular carcinoma (HBV-HCC) after TACE treatment based on systemic immune classification (SIC). A total of 80 patients with HBV-HCC were assessed for the peripheral blood immune exhaustion phenotype and immune proteins through a combination of “Olink High Sensitivity Plasma Proteomics” and “Multicolor Flow Cytometry.” An unsupervised clustering algorithm was employed to classify various immune subtypes and identify core indicators that evaluate the response of SIC to TACE treatment. The application of these two technologies as novel approaches for detecting HBV-HCC provides synergistic insights into disease mechanisms and patient prognosis. Based on the combination of immune exhaustion phenotypes and immune proteins, we developed SIC that classified the subjects into three clusters: Cluster 1, Cluster 2, and Cluster 3. Cluster 3 was associated with poor clinical characteristics, unfavorable prognosis, and elevated levels of immune checkpoint expression. This risk scoring system is capable of predicting the overall survival of patients at various time points, with receiver operating characteristic areas exceeding 0.8. This study establishes SIC method to predict the clinical response of HBV-HCC patients after TACE treatment, providing new guidance for future immunotherapy and identification of non-invasive biomarkers.

Flowchart depicting the process from HCC patient analysis to TACE treatment outcomes. It starts with FACS and PEA assays for immune cell phenotyping and proteomics. The results classify systemic immunity into three clusters: immune activated, intermediate, and immune exhausted. These classifications correlate with clinical responses to TACE treatment, shown as favorable, median, or worst, visualized in a survival curve chart.