Zhang Han, Xu Wenjin, Zhu Haitao, Chen Xuelian, Tsai Hsiang-I
Institute of Medical Imaging and Artificial Intelligence, Jiangsu University, Zhenjiang, China.
Department of Medical Imaging, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.
J Cancer. 2024 Feb 12;15(7):2003-2023. doi: 10.7150/jca.92502. eCollection 2024.
As a novel anticancer therapy, immunotherapy has demonstrated robust efficacy against a few solid tumors but poor efficacy against pancreatic ductal adenocarcinoma (PDAC). This poor outcome is primarily attributable to the intrinsic cancer cell resistance and T-cell exhaustion, which is also the reason for the failure of conventional therapy. The present review summarizes the current PDAC immunotherapy avenues and the underlying resistance mechanisms. Then, the review discusses synergistic combination therapies, such as radiotherapy (RT) and metabolic targeting. Research suggests that RT boosts the antigen of PDAC, which facilitates the anti-tumor immune cell infiltration and exerts function. Metabolic reprogramming contributes to restoring the exhausted T cell function. The current review will help in tailoring combination regimens to enhance the efficacy of immunotherapy. In addition, it will help provide new approaches to address the limitations of the immunosuppressive tumor microenvironment (TME) by examining the relationship among immunotherapy, RT, and metabolism targeting therapy in PDAC.
作为一种新型抗癌疗法，免疫疗法已在一些实体瘤中显示出强大疗效，但对胰腺导管腺癌（PDAC）疗效不佳。这种不良结果主要归因于癌细胞的内在抗性和T细胞耗竭，这也是传统疗法失败的原因。本综述总结了当前PDAC免疫治疗途径及潜在的抗性机制。然后，综述讨论了协同联合疗法，如放疗（RT）和代谢靶向治疗。研究表明，放疗可增强PDAC的抗原性，促进抗肿瘤免疫细胞浸润并发挥作用。代谢重编程有助于恢复耗竭的T细胞功能。本综述将有助于制定联合治疗方案以提高免疫治疗疗效。此外，通过研究PDAC中免疫治疗、放疗和代谢靶向治疗之间的关系，将有助于提供新方法来解决免疫抑制性肿瘤微环境（TME）的局限性。
