Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2018 Nov 13;19(11):3584. doi: 10.3390/ijms19113584.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of approximately 8%. More than 80% of patients are diagnosed at an unresectable stage due to metastases or local extension. Immune system reactivation in patients by immunotherapy may eliminate tumor cells and is a new strategy for cancer treatment. The anti-CTLA-4 antibody ipilimumab and anti-PD-1 antibodies pembrolizumab and nivolumab have been approved for cancer therapy in different countries. However, the results of immunotherapy on PDAC are unsatisfactory. The low response rate may be due to poor immunogenicity with low tumor mutational burden in pancreatic cancer cells and desmoplasia that prevents the accumulation of immune cells in tumors. The immunosuppressive tumor microenvironment in PDAC is important in tumor progression and treatment resistance. Switching from an immune tolerance to immune activation status is crucial to overcome the inability of self-defense in cancer. Therefore, thoroughly elucidation of the roles of various immune-related factors, tumor microenvironment, and tumor cells in the development of PDAC may provide appropriate direction to target inflammatory pathway activation as a new therapeutic strategy for preventing and treating this cancer.
胰腺导管腺癌 (PDAC) 是一种致命疾病，5 年生存率约为 8%。由于转移或局部扩散，超过 80%的患者在不可切除阶段被诊断出来。免疫疗法使患者的免疫系统重新激活，从而消除肿瘤细胞，这是癌症治疗的一种新策略。抗 CTLA-4 抗体伊匹单抗和抗 PD-1 抗体 pembrolizumab 和 nivolumab 已在不同国家批准用于癌症治疗。然而，免疫疗法在 PDAC 中的效果并不理想。低反应率可能是由于胰腺癌细胞肿瘤突变负担低和导致免疫细胞无法在肿瘤中聚集的纤维组织增生导致免疫原性差。PDAC 中的免疫抑制肿瘤微环境在肿瘤进展和治疗耐药性中起着重要作用。从免疫耐受状态转变为免疫激活状态对于克服癌症自身防御能力的丧失至关重要。因此，深入阐明各种免疫相关因素、肿瘤微环境和肿瘤细胞在 PDAC 发展中的作用，可能为靶向炎症通路激活提供适当的方向，作为预防和治疗这种癌症的新治疗策略。
