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Table 1 Biomarkers and cells in the breast cancer microenvironment

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

  1. ANG2 Angiopoietin 2, CAF Cancer-associated fibroblast, CTL Cytotoxic T lymphocyte, DCE Dynamic contrast enhanced, DOBI Dynamic optical breast imaging, EC Epithelial cell, EGF Epidermal growth factor, FGF Fibroblast growth factor, HEV High endothelial venules, ICB Immune checkpoint blockade, MDSC Myeloid-derived suppressor cell, MMP Matrix metallopeptidase, SWE Shear-wave elastography, TAM Tumor-associated macrophage, TME Tumor microenvironment, VEGF Vascular endothelial growth factor