Lee Belinda, Gibbs Peter
Division of Systems Biology & Personalized Medicine, Walter & Eliza Hall Institute (WEHI), Parkville, Victoria 3052, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
J Pers Med. 2019 Apr 26;9(2):20. doi: 10.3390/jpm9020020.
It is estimated that pancreatic cancer will be the second leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options for this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are not completely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, relatively poorer antigenicity compared to other solid tumors, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological, would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.
据估计,到2030年胰腺癌将成为全球癌症相关死亡的第二大主要原因,这凸显了针对这种毁灭性疾病目前仍缺乏有效的治疗选择。在胰腺癌中,缺乏可靠的预后或预测标志物来指导治疗决策,无论是对于全身化疗、分子靶向治疗还是免疫治疗。迄今为止,在未经选择的化疗难治性胰腺癌患者群体中,靶向药物和免疫治疗的结果均未达到预期。免疫疗法在胰腺癌中疗效不佳的原因尚未完全明确。胰腺癌面临的挑战包括肿瘤周围致密的促纤维增生性基质形成的物理屏障、趋化因子介导的T细胞排斥、与其他实体瘤相比相对较差的抗原性、肿瘤内浸润T细胞数量稀少,最终导致免疫抑制微环境。更好地理解炎症在胰腺癌中的作用、其肿瘤微环境以及个体患者相关特征,无论是分子、临床还是组织病理学特征,将有助于采取更有效的个性化方法来管理胰腺癌。在本综述中,将探讨炎症、免疫肿瘤微环境和潜在免疫生物标志物在胰腺癌中的作用。