Accumulating studies have clearly demonstrated high concentrations of extracellular ATP (eATP) within the tumor microenvironment (TME). Implications of these findings are multifold as ATP-mediated purinergic signaling has been shown to mediate a variety of cancer-related processes, including cell migration, resistance to cytotoxic therapy, and immune regulation. Broad roles of ATP within the tumor microenvironment are linked to the abundance of ATP-regulated purinergic receptors on cancer and stromal and various immune cell types, as well as on the importance of ATP release and signaling in the regulation of multiple cellular processes. ATP release and downstream purinergic signaling are emerging as a central regulator of tumor growth and an important target for therapeutic intervention. In this chapter, we summarize the major roles of purinergic signaling in the tumor microenvironment with a specific focus on its critical roles in the induction of immunogenic cancer cell death and immune modulation.
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