A New Era in Systemic Therapy for Hepatocellular Carcinoma: Atezolizumab plus Bevacizumab Combination Therapy

High levels of vascular endothelial growth factor (VEGF) released from hypoxic tumor cells and the vascular endothelium induce angiogenesis, thereby contributing to proliferation, invasion, and metastasis of cancer cells. In addition, VEGF promotes the recruitment and proliferation of various types of immunosuppressive cells, such as regulatory T-cells (Tregs), and the release of pro-tumor cytokines from these cells. VEGF also increases the recruitment of tumorassociated macrophages (TAMs), which increases the M2 phenotype activity at the tumor site. Recruited Tregs and TAMs also contribute to tumor proliferation by releasing VEGF and angiopoietin 2. Similarly, VEGF induces myeloid-derived suppressor cells (MDSCs), which also release VEGF. Meanwhile, VEGF has a suppressive effect on dendritic cells (DCs). It decreases the number of DCs and inhibits their maturation, thereby suppressing the antigen-presenting ability of DCs in the priming phase. Therefore, despite their presence, neoantigens are not presented on DCs, and the proliferation and activation of CD8-positive cells are impaired. In addition, cells upreguPublished online: March 5, 2020