Tan Elaine, El-Rayes Bassel
Department of Internal Medicine, Emory University School of Medicine, 100 Woodruff Circle Suite, 327, Atlanta, GA, 30322, USA.
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA.
J Gastrointest Cancer. 2019 Mar;50(1):1-8. doi: 10.1007/s12029-018-0179-z.
Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most aggressive and lethal diseases in the world. The success of immunotherapy in other types of malignancy has led to further trials to understand better the role of immunotherapy in PDAC. However, initial studies with immunotherapy, namely, the checkpoint inhibitors, in PDAC have not been met with the same outcomes. The purpose of this review is to identify and discuss the various resistance mechanisms of PDAC to immunotherapy (pancreatic stroma, genetic predisposition/epigenetics, and the immune inhibitory cells, cytokines, soluble factors, and enzymes that comprise the tumor microenvironment) and the solutions currently being studied to overcome them.
Various preclinical and early clinical studies have shown that immunotherapy, especially checkpoint inhibitors, in PDAC may be efficacious as part of a multi-modal treatment, in combination with other therapies that target these resistance mechanisms. Several clinical trials are ongoing to explore this concept further.
胰腺导管腺癌（PDAC）仍然是世界上最具侵袭性和致命性的疾病之一。免疫疗法在其他类型恶性肿瘤中的成功促使人们进行进一步试验，以更好地了解免疫疗法在PDAC中的作用。然而，在PDAC中使用免疫疗法（即检查点抑制剂）的初步研究并未取得相同的结果。本综述的目的是识别和讨论PDAC对免疫疗法的各种耐药机制（胰腺基质、遗传易感性/表观遗传学，以及构成肿瘤微环境的免疫抑制细胞、细胞因子、可溶性因子和酶），以及目前正在研究的克服这些机制的解决方案。
各种临床前和早期临床研究表明，免疫疗法，尤其是检查点抑制剂，在PDAC中作为多模式治疗的一部分，与针对这些耐药机制的其他疗法联合使用时可能有效。正在进行多项临床试验以进一步探索这一概念。
