Utilizing in vitro macrophage models, we verified that the process of M2 polarization is influenced by MTA signaling through the adenosine A2B receptor, resulting in upregulation of M2 marker genes Arg1, IL10, and Vegfa. This represents a unique mechanism of alternative macrophage activation and a potentially significant contribution to the immunosuppressive tumor microenvironment in GBM, which is known for an abundance of immunosuppressive tumor-associated macrophages71. This evidence concerns the gene ADORA2B and glioblastoma.