Targeting myeloid-derived suppressor cells in the treatment of hepatocellular carcinoma: current state and future perspectives

Li-Chun Lu,1–3 Chun-Jung Chang,1,2 Chih-Hung Hsu1–31Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan; 2Departments of Oncology, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Oncology, National Taiwan University Cancer Center, Taipei, TaiwanAbstract: Systemic therapy for advanced hepatocellular carcinoma (HCC) has been focusing on overcoming tumor angiogenesis and immunosuppression. Myeloid-derived suppressor cells (MDSCs) promote both angiogenesis and immunosuppression in the tumor microenvironment (TME). Multiple clinical studies have demonstrated the prognostic implications of and suggested the translational significance of MDSCs in patients with HCC. In preclinical HCC models, targeting MDSCs has been shown to enhance antitumor efficacy of sorafenib or immune checkpoint inhibitors. Reversing the protumor effects of MDSCs could be achieved by depleting MDSCs, blocking MDSC trafficking and migration into TME, and inhibiting the immunosuppressive functions of MDSCs. To date, these strategies have not yet been validated to be clinically useful in patients with malignancy including HCC. Future studies should focus on identifying specific markers for human MDSCs and developing combination approaches incorporating MDSC-targeting therapy in the treatment of HCC.Keywords: myeloid-derived suppressor cells, MDSCs; hepatocellular carcinoma, immunosuppression, angiogenesis, immunotherapy, immune checkpoint inhibito