Potentiating Cancer Immune Therapy via Nanomaterials and Purinergic Signaling

This is the authors' abstract. We don't add key points for this paper.

Adenosine, an autacoid nucleoside interacting with P1 receptors, activates four G protein-coupled receptors named A1, A2A, A2B, and A3, crucially regulating several human pathologies (Borea et al., 2018). It affects both neoplastic and immune cells, promoting cancer cell proliferation, neoangiogenesis, immunoescape, and metastasis (Arab and Hadjati, 2019). Extracellular nucleotides such as ATP, ADP, and UTP also function as cell-to-cell communication signals by binding and activating P2 receptors belonging to the P2X and P2Y subfamilies (Kennedy, 2021). These receptors are further subdivided into different subtypes (Khakh et al., 2021). The differential expressions of P1 and P2 receptors both in immune and tumor cells generate a complex picture. Cancers are able to convert extracellular ATP into immunosuppressive adenosine, through the activation of CD39 ectonucleotidase that hydrolyzes ATP to AMP, and a subsequent CD73 enzyme that transforms AMP into adenosine, with the stimulation of adenosine receptors on immune cells activating numerous immunosuppressive effects (Borea et al., 2018; Boison and Yegutkin 2019). The shift from P2 to P1 activation is important for limiting the inflammatory response, thus preventing tissue damage, but may also deleteriously inhibit immunosurveillance (Antonioli et al., 2013; Allard et al., 2019). Targeting CD39 and CD73 has, therefore, become a new way to fight cancer (Perrot et al., 2019; Moesta et al., 2020; Li et al., 2019). This review conjugates the current knowledge of purinergic signaling in cancer biology with techniques involving nanomaterials to increase anticancer immune responses.