Immune cell profiling predicts response to Atezolizumab-Bevacizumab in advanced hepatocellular carcinoma

초록

Background and aims: Atezolizumab combined with bevacizumab is the current frontline treatment for advanced hepatocellular carcinoma. Despite numerous studies, predicting patient response to this therapy remains challenging. Method: Patients with advanced hepatocellular carcinoma receiving atezolizumab-bevacizumab therapy were enrolled. Blood samples were taken at baseline and two weeks after treatment initiation. Peripheral blood mononuclear cells (PBMCs) were isolated for analysis. Eight patients were selected based on initial response: four responders (complete or partial response) and four nonresponders (progressive disease). Single-cell RNA sequencing (scRNA-seq) was performed on the PBMC samples. Results: Patients with favorable prognoses exhibited higher frequencies of γδ T cells, CD4+ T cells, CD8+ T cells, and both classical and non-classical monocytes in their peripheral blood mononuclear cells (PBMCs) before treatment compared to those with poor prognoses. After treatment, patients with positive outcomes showed a notable increase in proliferating lymphocytes. Importantly, a specific subpopulation of CD8+ T cells, designated as cluster 4, emerged as a potential biomarker for treatment response. This cluster, characterized by high expression of the proliferation marker MKI67 and inhibitory checkpoint genes such as PDCD1, HAVCR2, and CTLA4, was more prevalent in the pre-treatment PBMCs of patients with favorable prognoses. Moreover, patients with better outcomes exhibited a significant increase in the frequency of this cluster after treatment, suggesting its potential role in predicting and mediating response to the combination therapy. Conclusion: This study mapped the diverse circulating immune cell populations in advanced hepatocellular carcinoma patients before and after atezolizumab-bevacizumab treatment. A distinct subgroup of CD8+ T cells emerged as a promising biomarker for predicting treatment response, potentially aiding in personalized therapy decisions for this aggressive cancer.