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Purines and pyrimidines are signaling molecules in the tumor microenvironment that affect cancer immunity. The purinergic signaling pathways have been shown to play an important role in the development and progression of cancer. CD39 and CD73 are ectonucleotidases responsible for breaking down ATP or ADP into adenosine, which regulates immunosuppression in various types of cancer. These enzymes have been studied as a potential therapeutic target in immunotherapy, and recent research suggests a correlation between ectonucleotidases and clinical outcomes in cancer.Prostate cancer is the most diagnosed cancer in men, after non-melanoma skin tumors, and is the second leading cause of death in men in the world. Despite having long survival periods, patients often receive excessive or insufficient treatment. Within this complex landscape, the adenosine/CD73 pathway plays a crucial role. Therefore, this review aims to highlight new findings on the potential role of purinergic signaling in cancer treatment and emphasizes the importance of anti-CD73 as a pharmacological strategy for prostate cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gardani, Diz, Dondé, Rockenbach, Laufer and Morrone.)

Glioblastoma is the most malignant and lethal subtype of glioma. Despite progress in therapeutic approaches, issues with the tumor immune landscape persist. Multiple immunosuppression pathways coexist in the tumor microenvironment, which can determine tumor progression and therapy outcomes. Research in immune checkpoints, such as the PD-1/PD-L1 axis, has renewed the interest in immune-based cancer therapies due to their ability to prevent immunosuppression against tumors. However, PD-1/PD-L1 blockage is not completely effective, as some patients remain unresponsive to such treatment. The production of adenosine is a major obstacle for the efficacy of immune therapies and is a key source of innate or adaptive resistance. In general, adenosine promotes the pro-tumor immune response, dictates the profile of suppressive immune cells, modulates the release of anti-inflammatory cytokines, and induces the expression of alternative immune checkpoint molecules, such as PD-1, thus maintaining a loop of immunosuppression. In this context, this review aims to depict the complexity of the immunosuppression in glioma microenvironment. We primarily consider the PD-1/PD-L1 axis and adenosine pathway, which may be critical points of resistance and potential targets for tumor treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Scheffel, Grave, Vargas, Diz, Rockenbach and Morrone.)

The release of damage-associated molecular patterns, including uridine triphosphate (UTP) and adenosine triphosphate (ATP) to the extracellular milieu is a key component of innate immune response to infection. Previously, we showed that macrophage infection by the protozoan parasite Leishmania amazonensis -the etiological agent of cutaneous leishmaniasis-can be controlled by ATP- and UTP-mediated activation of P2Y and P2X7 receptors (activated by UTP/ATP and ATP, respectively), which provided comparable immune responses against the parasite. Interestingly, in context of Leishmania amazonensis infection, UTP/P2Y triggered apoptosis, reactive oxygen species, and oxide nitric (NO) production, which are characteristic of P2X7 receptor activation. Here, we examined a possible "cross-talk" between P2Y 2 and P2X7 receptors, and the requirement for pannexin-1 (PANX-1) in the control of L. amazonensis infection in mouse peritoneal macrophages and in vivo . UTP treatment reduced L. amazonensis parasite load, induced extracellular ATP release [which was pannexin-1 (PANX-1) dependent], and triggered leukotriene B 4 (LTB 4 ) production in macrophages. UTP-induced parasite control was blocked by pharmacological antagonism of P2Y 2 or P2X7 receptors and was absent in macrophages lacking P2X7 or PANX-1. In addition, ATP release induced by UTP was also inhibited by PANX-1 blocker carbenoxolone, and partially reversed by inhibitors of vesicle traffic and actin cytoskeleton dynamics. In vivo , UTP treatment reduced footpad and popliteal lymph node parasite load, and the lesion in wild-type (WT) mice; fact not observed in P2X7 -/- mice. Our data reveal that P2Y 2 and P2X7 receptors cooperate to trigger potent innate immune responses against L. amazonensis infection.