Gan Li-Lian, Hii Ling-Wei, Wong Shew-Fung, Leong Chee-Onn, Mai Chun-Wai
School of Postgraduate Study, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
Cancers (Basel). 2020 Jul 11;12(7):1872. doi: 10.3390/cancers12071872.
Pancreatic cancer ranks high among the causes of cancer-related mortality. The prognosis of this grim condition has not improved significantly over the past 50 years, despite advancement in imaging techniques, cancer genetics and treatment modalities. Due to the relative difficulty in the early detection of pancreatic tumors, as low as 20% of patients are eligible for potentially curative surgery; moreover, chemotherapy and radiotherapy (RT) do not confer a great benefit in the overall survival of the patients. Currently, emerging developments in immunotherapy have yet to bring a significant clinical advantage among pancreatic cancer patients. In fact, pancreatic tumor-driven immune evasion possesses one of the greatest challenges leading to immunotherapeutic resistance. Most of the immune escape pathways are innate, while poor priming of hosts' immune response and immunoediting constitute the adaptive immunosuppressive machinery. In this review, we extensively discuss the pathway perturbations undermining the anti-tumor immunity specific to pancreatic cancer. We also explore feasible up-and-coming therapeutic strategies that may restore immunity and address therapeutic resistance, bringing hope to eliminate the status quo in pancreatic cancer prognosis.
胰腺癌在癌症相关死亡原因中位居前列。尽管在成像技术、癌症遗传学和治疗方式方面取得了进展，但在过去50年里，这种严峻疾病的预后并未得到显著改善。由于胰腺肿瘤早期检测相对困难，只有20%的患者有资格接受可能治愈性的手术；此外，化疗和放疗对患者的总体生存率并没有带来很大益处。目前，免疫疗法的新进展尚未给胰腺癌患者带来显著的临床优势。事实上，胰腺肿瘤驱动的免疫逃逸是导致免疫治疗耐药性的最大挑战之一。大多数免疫逃逸途径是先天性的，而宿主免疫反应的启动不良和免疫编辑构成了适应性免疫抑制机制。在这篇综述中，我们广泛讨论了破坏胰腺癌特异性抗肿瘤免疫的信号通路扰动。我们还探索了可行的新兴治疗策略，这些策略可能恢复免疫力并解决治疗耐药性问题，为消除胰腺癌预后的现状带来希望。
