THE COMPOSITION OF CIRCULATING IMMUNE CELLS FOLLOWING TREATMENT WITH ATEZOLIZUMAB AND BEVACIZUMAB IN ADVANCED HEPATOCELLULAR CARCINOMA

초록

Background: Currently, combination therapy of atezolizumab and bevacizumab is used as a first-line therapy for advanced hepatocellular carcinoma. Numerous studies were performed to predict the response to this combination therapy, but it is still unknown. Methods: Patients with advanced hepatocellular carcinoma undergoing atezolizumab and bevacizumab combination therapy were enrolled in this study. Blood samples were collected on days 0 and 14 of the first administration of atezolizumab and bevacizumab. Peripheral blood mononuclear cells (PBMC) were isolated from blood samples. Eight patients were selected after the first response study; 4 showed complete response or partial response, and 4 showed progressive disease response. scRNA-seq was performed using previously collected PBMC samples. Results: Before treatment, patients with a positive prognosis typically showed elevated frequencies of γδ T cells, CD4+ T cells, classical monocytes, CD8+ T cells, and non-classical monocytes in their PBMCs compared to those with a less favorable prognosis. Additionally, a notable increase in proliferating lymphocytes was observed post-treatment among patients with a favorable prognosis. In the CD8+ T cell subset, cluster 4, characterized by high expression of the proliferation marker MKI67 and inhibitory checkpoint genes like PDCD1, HAVCR2, and CTLA4, is more prevalent in patients with favorable prognosis in PBMCs before treatment. Moreover, patients with better prognosis exhibit a notable increase in the frequency of this cluster after treatment. Conclusion: The landscape of heterogenous circulating immune cells of patients with advanced hepatocellular carcinoma before and after atezolizumab and bevacizumab treatment was identified in this study. A subgroup of CD8+ T cells can be a biomarker for predicting the response to combination treatment.