Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, P. R. China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, 310003, P. R. China.
Adv Sci (Weinh). 2023 Apr;10(10):e2206756. doi: 10.1002/advs.202206756. Epub 2023 Jan 25.
Pancreatic ductal adenocarcinoma rapidly acquires resistance to chemotherapy, remaining a fatal disease. Immunotherapy is one of the breakthroughs in cancer treatment, which includes immune checkpoint inhibitors, chimeric antigen receptor T-cell immunotherapy, and neoantigen vaccines. However, immunotherapy has not achieved satisfactory results in the treatment of pancreatic cancer. Immunogenic death comprises proinflammatory cell death, which provides a way to enhance tumor immunogenicity and promote an immune response in solid tumors. Herein, an ionic liquid ablation agent (LAA), synthesized from choline and geranic acid, which triggers necrosis-induced immunotherapy by remodeling an immunosuppressive "cold" tumor to an immune activated "hot" tumor is described. The results indicate that LAA-treated tumor cells can enhance immunogenicity, inducing dendritic cell maturation, macrophage M1 polarization, and cytotoxic T lymphocyte infiltration. The results of the present study provide a novel strategy for solid tumor immunotherapy.
胰腺导管腺癌迅速对化疗产生耐药性，仍是一种致命疾病。免疫疗法是癌症治疗的突破之一，包括免疫检查点抑制剂、嵌合抗原受体 T 细胞免疫疗法和新抗原疫苗。然而，免疫疗法在胰腺癌治疗中尚未取得满意的效果。免疫原性细胞死亡包括促炎细胞死亡，它为增强肿瘤免疫原性和促进实体瘤中的免疫反应提供了一种方法。在此，描述了一种由胆碱和香叶酸合成的离子液体消融剂 (LAA)，它通过重塑免疫抑制的“冷”肿瘤为免疫激活的“热”肿瘤，从而引发坏死诱导的免疫疗法。结果表明，LAA 处理的肿瘤细胞可以增强免疫原性，诱导树突状细胞成熟、巨噬细胞 M1 极化和细胞毒性 T 淋巴细胞浸润。本研究结果为实体瘤免疫治疗提供了一种新策略。
