Furthermore, stimulation of A2AR, on macrophages populating the tumor lesion, promotes the differentiation of M2-like macrophages, which are the major responsible for the accumulation of vascular endothelial growth factor (VEGF) in the TME and the subsequential angiogenesis (Sitkovsky et al., 2014; Allard et al., 2020). This evidence concerns the gene ADORA2A and neoplasm.