Pham Thao N D, Shields Mario A, Spaulding Christina, Principe Daniel R, Li Bo, Underwood Patrick W, Trevino Jose G, Bentrem David J, Munshi Hidayatullah G
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Jesse Brown VA Medical Center, Chicago, IL 60612, USA.
Cancers (Basel). 2021 Jan 25;13(3):440. doi: 10.3390/cancers13030440.
The advent of immunotherapy has transformed the treatment landscape for several human malignancies. Antibodies against immune checkpoints, such as anti-PD-1/PD-L1 and anti-CTLA-4, demonstrate durable clinical benefits in several cancer types. However, checkpoint blockade has failed to elicit effective anti-tumor responses in pancreatic ductal adenocarcinoma (PDAC), which remains one of the most lethal malignancies with a dismal prognosis. As a result, there are significant efforts to identify novel immune-based combination regimens for PDAC, which are typically first tested in preclinical models. Here, we discuss the utility and limitations of syngeneic and genetically-engineered mouse models that are currently available for testing immunotherapy regimens. We also discuss patient-derived xenograft mouse models, human PDAC organoids, and ex vivo slice cultures of human PDAC tumors that can complement murine models for a more comprehensive approach to predict response and resistance to immunotherapy regimens.
免疫疗法的出现改变了多种人类恶性肿瘤的治疗格局。针对免疫检查点的抗体，如抗PD-1/PD-L1和抗CTLA-4，在多种癌症类型中显示出持久的临床益处。然而，检查点阻断在胰腺导管腺癌（PDAC）中未能引发有效的抗肿瘤反应，胰腺导管腺癌仍然是最致命的恶性肿瘤之一，预后很差。因此，人们正在大力寻找用于PDAC的基于免疫的新型联合治疗方案，这些方案通常首先在临床前模型中进行测试。在这里，我们讨论了目前可用于测试免疫治疗方案的同基因和基因工程小鼠模型的效用和局限性。我们还讨论了患者来源的异种移植小鼠模型、人PDAC类器官以及人PDAC肿瘤的离体切片培养，这些可以补充小鼠模型，以采用更全面的方法来预测对免疫治疗方案的反应和耐药性。
