DelGiorno Kathleen
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Res. 2023 Apr 4;83(7):977-978. doi: 10.1158/0008-5472.CAN-23-0268.
Molecular stratification of patients with pancreatic ductal adenocarcinoma (PDAC) has the potential to guide clinical decision-making for therapeutic intervention. Investigating mechanisms by which different molecular subtypes of PDAC form and progress will improve patient responses to existing therapies and aid in identifying new, more specific therapeutic approaches. In this issue of Cancer Research, Faraoni and colleagues identified CD73/Nt5e-generated adenosine as a mechanism of immunosuppression specifically in pancreatic ductal-derived basal/squamous-type PDAC. Using genetically engineered mouse models targeting key genetic mutations to pancreatic acinar or ductal cells and an array of experimental and computational biology approaches, the authors found that adenosine signaling through receptor ADORA2B induces immunosuppression and tumor progression in ductal cell-derived tumors. These data demonstrate how molecular stratification of PDAC in combination with targeted approaches may enhance patient responses to therapy in this deadly cancer. See related article by Faraoni et al., p. 1111.
胰腺导管腺癌（PDAC）患者的分子分层有潜力指导治疗干预的临床决策。研究PDAC不同分子亚型形成和进展的机制，将改善患者对现有疗法的反应，并有助于确定新的、更具特异性的治疗方法。在本期《癌症研究》中，法拉奥尼及其同事确定了CD73/Nt5e生成的腺苷是胰腺导管来源的基底/鳞状型PDAC中一种特异性免疫抑制机制。通过针对胰腺腺泡或导管细胞关键基因突变的基因工程小鼠模型以及一系列实验和计算生物学方法，作者发现通过受体ADORA2B的腺苷信号传导在导管细胞来源的肿瘤中诱导免疫抑制和肿瘤进展。这些数据证明了PDAC的分子分层与靶向方法相结合如何可能增强这种致命癌症患者对治疗的反应。见法拉奥尼等人的相关文章，第1111页。
