Department of Urology, Ulm University Hospital, 89081 Ulm, Germany.
Department of Internal Medicine I, Ulm University Hospital, 89081 Ulm, Germany.
Int J Mol Sci. 2020 May 8;21(9):3345. doi: 10.3390/ijms21093345.
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Different factors such as mutational landscape, intra- and intertumoral heterogeneity, stroma, and immune cells impact carcinogenesis of PDAC associated with an immunosuppressive microenvironment. Different cell types with partly opposing roles contribute to this milieu. In recent years, immunotherapeutic approaches, including checkpoint inhibitors, were favored to treat cancers, albeit not every cancer entity exhibited benefits in a similar way. Indeed, immunotherapies rendered little success in pancreatic cancer. In this review, we describe the communication between the immune system and pancreatic cancer cells and propose some rationale why immunotherapies may fail in the context of pancreatic cancer. Moreover, we delineate putative strategies to sensitize PDAC towards immunological therapeutics and highlight the potential of targeting neoantigens.
胰腺导管腺癌 (PDAC) 的预后仍然很差。不同的因素,如突变景观、肿瘤内和肿瘤间异质性、基质和免疫细胞,影响与免疫抑制微环境相关的 PDAC 的发生。具有部分相反作用的不同细胞类型有助于这种环境。近年来,免疫治疗方法,包括检查点抑制剂,被用于治疗癌症,尽管并非每种癌症实体都以相似的方式受益。事实上,免疫疗法在胰腺癌中的效果甚微。在这篇综述中,我们描述了免疫系统和胰腺癌细胞之间的相互作用,并提出了一些免疫疗法在胰腺癌中可能失败的原因。此外,我们还描述了一些使 PDAC 对免疫治疗敏感的策略,并强调了针对新抗原的潜在可能性。