Fig. 2

Antiangiogenic therapy combined with immunotherapy improves the tumor immune microenvironment (created with BioRender.com). In breast cancer, antiangiogenic therapy (bevacizumab or VEGFR-TKI) induces tumor vascular normalization, improves blood perfusion, and promotes immune cell recruitment and dendritic cell (DC) maturation. The immunosuppressive state is further relieved using immune checkpoint inhibitors (anti-PD-1/PD-L1 monoclonal antibodies, mAbs). After A + I combination therapy, the immunosuppressive microenvironment is transformed into an immune-supporting microenvironment with increased numbers of M1-like macrophages, mature DCs, CD8+ CTLs, Th1 CD4+ T cells, and activated NK cells and decreased numbers of Tregs, thus effectively exerting an antitumor effect. CTL, Cytotoxic T cell; ANG2, Angiopoietin 2; DC, Dendritic cell; Fas-L, FAS antigen ligand; FGF, Fibroblast growth factor; MMP, Matrix metallopeptidase; NK, Natural killer; PD-1, Programmed cell death protein 1; PD-L1, Programmed cell death 1 ligand 1; TAM, Tumor-associated macrophage; TME, Tumor microenvironment; Tregs, Regulatory T cells; VEGF, Vascular endothelial growth factor