Figure 8.

The relevant mechanisms of PD-1/PD-L1 inhibitors plus anti-angiogenic agents. T cells can be suppressed by members of the VEGF family, and VEGF can augment the suppressive actions of ImDCs, Tregs, TAMs, and MDSCs, which prevent T cells from having an anti-tumor impact. Anti-angiogenic agents inhibit the VEGF signaling pathway, which in turn activates T cells. T cells improve the tumor microenvironment by releasing IFN-γ, and IFN-γ upregulates chemokine CXC ligands 9, 10, and 11 to promote normalization of tumor vessels, thereby attenuating the effect of VEGF. PD-1/PD-L1 signaling pathway attenuates the anti-tumor activity of T cells, PD-1/PD-L1 inhibitors reactivate the anti-tumor activity of T cells, T cells improve the tumor microenvironment by releasing IFN-γ, IFN-γ upregulates chemokine CXC ligands 9, 10 and 11 to promote normalization of tumor vessels, thereby attenuating the effect of VEGF, which form a positive feedback loop between immunotherapy and anti-angiogenic therapy. VEGF, Vascular Endothelial Growth Factor; ImDCs, Immature Dendritic Cells; Treg, Regulatory T cells; TAMs, Tumor Associated Macrophages; MDSCs, Myeloid Derived Suppressor Cells. IFN-γ, Interferon-γ.