Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and highly lethal malignancies. Existing therapeutic interventions have so far been unsuccessful in improving prognosis, and survival remains very poor. Oncolytic virotherapy represents a promising, yet not fully explored, alternative strategy for the treatment of PDAC. Oncolytic viruses (OVs) infect, replicate within and lyse tumor cells specifically and stimulate antitumor immune responses. Multiple challenges have hampered the efficacy of oncolytic virotherapy for PDAC, the most significant being the desmoplastic and immunosuppressive pancreatic tumor microenvironment (TME). The TME limits the access of therapeutic drugs and the infiltration of effector T cells and natural killer (NK) cells into the tumor mass. Additionally, cancer cells promote the secretion of immunosuppressive factors and develop mechanisms to evade the host immune system. Because of their oncolytic and immune-stimulating properties, OVs are the ideal candidates for counteracting the pancreatic immunosuppressive TME and for designing combination therapies that can be clinically exploited in clinical trials that seek to improve the prognosis of PDAC.

胰腺导管腺癌 (PDAC) 是最具侵袭性和高度致命的恶性肿瘤之一。迄今为止，现有的治疗干预措施未能成功改善预后，存活率仍然很差。溶瘤病毒疗法代表了一种有前途但尚未完全探索的 PDAC 治疗替代策略。溶瘤病毒 (OVs) 感染、复制和特异性裂解肿瘤细胞并刺激抗肿瘤免疫反应。多重挑战阻碍了溶瘤病毒疗法对 PDAC 的疗效，其中最重要的是促结缔组织增生和免疫抑制性胰腺肿瘤微环境 (TME)。TME 限制了治疗药物的获取以及效应 T 细胞和自然杀伤 (NK) 细胞向肿瘤块的浸润。此外，癌细胞促进免疫抑制因子的分泌，并发展出逃避宿主免疫系统的机制。由于它们的溶瘤和免疫刺激特性，OVs 是对抗胰腺免疫抑制性 TME 和设计联合疗法的理想候选者，这些疗法可以在临床试验中用于寻求改善 PDAC 预后的临床试验。