From: Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment
TME elements | Function |
M1-like TAMs | Suppress angiogenesis (IL-12 and TNF-α); Induce vascular maturation |
M2-like TAMs | Promote angiogenesis (VEGF-A, EGF and FGF); Enhance ECs migration and proliferation; Polarize M1-like into M2-like TAMs |
Mature dendritic cells | Suppress angiogenesis (IL-12 and IL-18); inhibit EC proliferation |
Immature dendritic cells | Lack the ability to inhibit angiogenesis |
CD8+ CTLs | Suppress angiogenesis (IFN-γ) |
Th1 cells | Suppress angiogenesis (IFN-γ); improve pericyte coverage |
Th2 cells | Promote angiogenesis (IL-4, IL-5 and IL-13); recruit M2-like TAMs |
Th17 cells | Promote angiogenesis (IL-17); promote ECs proliferation |
Tregs | Promote angiogenesis (VEGF); inhibit Th1 cell activation; promote M2-like TAMs |
MDSCs | Promote angiogenesis (VEGF, FGF2, Bv8 and MMP9); acquire endothelial cell properties |
CAFs | Promote angiogenesis (VEGF, CXC12, SDF1 and PDGF-c); enhance VEGF expression (PDPN and LGALS1); release ECM-bound VEGF |
Serum-based biomarkers | Function |
ANG2 and VEGF-A | Key factor of angiogenesis; predict long-term remission and survival |
Tissue-based biomarkers | Function |
HEVs | Specialized vascular units organized in tertiary lymphoid structures; help immature T cells differentiate into CTLs; the formation of HEVs indicates the improvement of ICB immunotherapy efficacy |
TME model | Investigate the complex interactions between tumor cells, immune cells (M1/M2-like TAMs, NK cells, CD4+ / CD8+ T cells, and Tregs), and endothelial cells; assess tissue perfusion and predict immunotherapy efficacy |
Noninvasive measures (DCE-MRI, DOBI, SWE) | Measure vascular changes and provide information on TME status |