In addition to tumor cell intrinsic signaling (1), tumor-derived 2’, 3’-cGAMP can be recognized by leukocytes such as CD11b+ and B cells and subsequently activate STING, inducing type I interferon production by the leukocytes to prime NK cells for cytotoxic killing of tumor cells (2). Intercellular gap junctions enable transfer of this second messenger in adjacent cells, which has been linked to metastasis (3). It is also well established that the tumor vasculature responds to cyclic dinucleotides, though how this impacts the tumor microenvironment is poorly understood (4). Finally, STING activation in leukocytes or other cells by 2’, 3’-cGAMP could also promote production of immunosuppressive cytokines such as CCL2, which can recruit myeloid-derived suppressor cells (MDSCs) (5). Red = anti-tumorigenic effects and blue = potential pro-tumorigenic effects of STING agonism in the tumor microenvironment.