Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-0621's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Hs-510's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
Cancer Treat Rev. 2014 May;40(4):513-22. doi: 10.1016/j.ctrv.2013.11.005. Epub 2013 Nov 23.
Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials.
传统的化疗在提高胰腺癌患者生存率方面收效甚微。胰腺癌对强化治疗具有较强抵抗力的原因之一是，癌症能够劫持免疫系统：在疾病进展过程中，免疫系统从攻击肿瘤细胞的系统转变为癌症的支持结构，对癌细胞发挥营养作用。这种免疫系统作用的转变是通过调节性 T 细胞、髓源性抑制细胞、肿瘤相关巨噬细胞和成纤维细胞的动员和激活来实现的，所有这些细胞都抑制 CD8 T 细胞和 NK 细胞。这种免疫抑制既通过表达诱导耐受的细胞表面分子（如 PD-L1），也通过产生“耐受原性”细胞因子（如 IL-10 和 TGF-β）来实现。基于对免疫系统对胰腺癌患者预后重要性的认识不断增加，目前正在临床试验中测试多种针对胰腺癌的新免疫治疗方法。在这篇综述中，我们概述了胰腺癌的免疫逃逸机制以及目前正在胰腺癌临床试验中测试的新的免疫相关治疗策略。
