Tumor vascular endothelial cells and tumor-associated macrophages (TEC/TAM)

Tumor vascular endothelial cells (TECs) and tumor-associated macrophages (TAMs) are two critical, non-malignant cell populations within the tumor microenvironment (TME) that cooperate to drive cancer progression [4, 6]. TECs form the aberrant, leaky vasculature that provides nutrients and a route for metastasis, while TAMs (particularly M2-polarized macrophages) secrete pro-angiogenic factors and create an immunosuppressive niche that protects the tumor from immune attack [3, 5]. The concept of dually targeting these populations has gained traction because of their intense crosstalk; for instance, TAMs produce VEGF and Angiopoietin-2 to stimulate TECs, and TECs express adhesion molecules that recruit TAM precursors [5, 6]. Therapeutic strategies targeting this axis often focus on shared molecular markers or pathways, such as the Tie2 receptor, the CSF1R/VEGFR signaling network, or the enzyme legumain, which is highly expressed on the surface of both cell types in the TME [1, 2, 5]. By simultaneously disrupting the tumor's blood supply and relieving local immunosuppression, these therapies aim to overcome the limitations and resistance mechanisms associated with targeting either cell type alone [5, 6].

Other names

Tumor-associated endothelial cells and macrophagesTumor stromaTie2-expressing stromal cellsLegumain-expressing tumor microenvironment cells

Dual inhibition of pro-angiogenic and immunosuppressive signaling pathways (e.g., VEGF, Ang2, CSF1R), depletion of tumor-supporting stromal cells, and proteolytic activation of prodrugs by cell-surface enzymes like legumain.