Adenosine, along with critically contributing to the establishment of a tolerogenic TME, also enables tumors to subvert fibroblasts into supporting them and to induce formation of new blood vessels, processes essential to their growth and dissemination. CAFs, for example, are stromal cells that support tumors by secreting the pro-metastatic and angiogenic (316) chemokine CXCL12 (317), as well as the mitogenic (318) fibroblast growth factor 2 (FGF2) (319). Triggering of A2BR on the surface of CAFs boosts expression of both CXCL12 and FGF2 (320) whereas A2AR-induced signaling stimulates their proliferation (54). As previously mentioned, adenosine can stimulate VEGF secretion by multiple cell types found within the TME, which in turn promotes angiogenesis by supporting the survival, migration and proliferation of endothelial cells (321, 322). It has also been shown that A2AR (323) and A2BR (66) stimulation diminishes production of the anti-angiogenic factor thrombospondin-1 by endothelial cells. Furthermore, adenosine not only augments the rate of intra-tumoral nutrient delivery by inducing vasodilatation (324), but also hinders leukocyte extravasation (325) through downregulation of adhesion molecules, such as E-selectin (326, 327) VCAM-1 (326, 327) and ICAM-1 (327, 328) on the surface of endothelial cells, as well as by limiting vascular permeability (325, 327, 329–331) through A2BR activation (329–331). Finally, signaling initiated by triggering of A2AR (332, 333), A2BR (334–336) or non-specified ARs prompts endothelial cells to overexpress CD73 (334) as well as the proangiogenic factors VEGF (332, 333, 335, 336), IL-8 (335) and basic fibroblast growth factor (bFGF) (335, 336).