P2 Purinergic Receptors in Tumor Immunity.

P2 purinergic receptors are activated by extracellular adenosine triphosphate and other nucleotides released during cellular stress, hypoxia, or inflammation, serving as key mediators of intercellular communication. In cancer, they rapidly accumulate in the tumor microenvironment following cell death or metabolic stress. Activation of the P2 purinergic receptors P2X and P2Y can trigger both pro-inflammatory and immunosuppressive responses, and emerging evidence underscores P2 purinergic signaling as a central immunomodulator in cancer, critically shaping tumor immunobiology by coordinating immune cell interactions. This review explores how P2 purinergic signaling drives tumor progression through microenvironmental crosstalk and highlights therapeutic strategies targeting the pathway to disrupt pro-tumorigenic networks.