Issues

Immunoprevention is an emerging approach to solid tumors such as pancreatic ductal adenocarcinoma (PDAC), and pancreatic intraepithelial neoplasia (PanIN) are precursor lesions present in healthy pancreas. However, not all PanIN lesions progress into PDAC, indicating a window in opportunity for the utilization of immunoprevention therapies to enhance antitumor immune cell surveillance. Present on PanIN lesions, CD73 is an ectoenzyme that generates immunosuppressive extracellular adenosine. In this study starting on page 456, Strickland and colleagues used a small molecule CD73 inhibitor to target CD73-generated adenosine production and found PanIN progression was prevented. The cover image is adapted from Fig. 2, which shows decreases in fibrosis, proliferation, and PanIN progression with treatment of CD73 small molecule inhibitor, AB-680. CD73 inhibition is also associated with changes in macrophage polarization state as well as TCR and BCR rearrangement and clonal expansion. These results indicate that CD73 inhibitor AB-680 could be used as an immunopreventive agent to prevent progression from PanIN to PDAC in high-risk populations.