Transcatheter Arterial Embolization Containing Donafenib Induces Anti-Angiogenesis and Tumoricidal CD8+ T-Cell Infiltration in Rabbit VX2 Liver Tumor

Abstract

Qin Shi,1,2,* Tongqiang Li,1,2,* Songjiang Huang,1,2,* Yaowei Bai,1,2 Yingliang Wang,1,2 Jiacheng Liu,1,2 Chen Zhou,1,2 Yang Chen,1,2 Bin Xiong1,2 1Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin XiongDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, People’s Republic of ChinaEmail [email protected]: To evaluate the effect and immune response of transcatheter arterial embolization (TAE) combined with donafenib in rabbit VX2 liver tumor model.Materials and Methods: Thirty-six New Zealand white rabbits with VX2 liver tumor were randomly divided into three groups. The LD group was treated with the emulsion of 0.5 mL lipiodol and 4 mg donafenib via hepatic arterial administration. The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The control group was treated with the equal volume of saline. Four rabbits were euthanized in each group on day 1, 3 and 7 after treatment. The tumor growth, histological markers associated with angiogenesis and immune response were assessed by imaging and histopathology. In addition, immune modulatory cytokines included interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and biochemical hepatorenal function were measured.Results: Compared to other groups, LD group achieved lower tumor growth rate, fewer metastatic lesions, and higher tumor necrosis rate on day 7 after treatment. The percentage of CD31-positive area in the LD group was significantly lower than that in the LE group on day 3 and 7 after treatment. In addition, CD8+ lymphocytes infiltration was more pronounced in LD group than in LE group on day 7 after treatment, regardless of in the tumor or adjacent liver tissue. Serum cytokines including IL-6, TNF-α and IFN-γ were strongly upregulated in the LD group on day 1 after treatment. And there was no significant difference in the hepatorenal function between LD group and LE group after treatment.Conclusion: The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer.Keywords: liver cancer, transcatheter arterial embolization, donafenib, tumor angiogenesis, immune response

Keywords

• liver cancer
• transcatheter arterial embolization
• donafenib
• tumor angiogenesis
• immune response