Department of Medicine, Division of Hematology/Oncology, East Carolina University Brody School of Medicine, Greenville, NC 27834, USA.
Department of Surgery, Division of Surgical Oncology, East Carolina University Brody School of Medicine, Greenville, NC 27834, USA.
Int J Mol Sci. 2018 Nov 7;19(11):3505. doi: 10.3390/ijms19113505.
Immune checkpoint blockade (ICB) with programmed cell death protein-1(PD-1)/programmed death ligand -1(PD-L1) antibodies has revolutionized the management of several cancers, especially non-small cell lung cancer, melanoma, urothelial, and renal cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with high morbidity and mortality. Based on available data, it's obvious that ICB has limited success in PDACs, which can be explained by the low immunogenicity and immunosuppressive tumor microenvironment of these tumors. In this review article, we focus on PD-L1 expression and microsatellite instability (MSI) in PDAC, and their roles as prognostic and predictive markers. We also discuss data supporting combination therapies to augment cancer immunity cycle. Combining anti-PD-1/PD-L1 agents with other modalities such as vaccines, chemotherapy, and radiation could potentially overcome resistance patterns and increase immune responsiveness in PDAC.
免疫检查点阻断(ICB)联合程序性死亡蛋白-1(PD-1)/程序性死亡配体-1(PD-L1)抗体已经彻底改变了多种癌症的治疗方法,特别是非小细胞肺癌、黑色素瘤、尿路上皮癌和肾癌。胰腺导管腺癌(PDAC)是一种侵袭性很强的癌症,其发病率和死亡率都很高。根据现有数据,ICB 在 PDAC 中的应用效果有限,这可以解释为这些肿瘤的免疫原性低和免疫抑制性肿瘤微环境。在这篇综述文章中,我们重点关注 PDAC 中的 PD-L1 表达和微卫星不稳定性(MSI),以及它们作为预后和预测标志物的作用。我们还讨论了支持联合治疗以增强癌症免疫循环的数据。将抗 PD-1/PD-L1 药物与疫苗、化疗和放疗等其他方法联合使用,可能有助于克服耐药模式,提高 PDAC 的免疫反应性。