Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Colorectal Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Aging (Albany NY). 2020 Dec 19;13(1):1383-1409. doi: 10.18632/aging.202355.
Combination therapies based on photodynamic therapy (PDT) have received much attention in various cancers due to their strong therapeutic effects. Here, we aimed to explore the safety and effectiveness of a new mitochondria-targeting photodynamic material, TPE-IQ-2O, in combination therapies (combined with surgery or immunotherapy). The safety and effectiveness of TPE-IQ-2O PDT were verified with cytotoxicity evaluation and a zebrafish xenograft model , respectively. The effectiveness of TPE-IQ-2O PDT combined with surgery or immune checkpoint inhibitors (ICIs) was verified in tumor-bearing mice. Small animal imaging, immunohistochemistry, and flow cytometry were used to determine the underlying mechanism. TPE-IQ-2O PDT can not only reduce tumor recurrence in surgical treatment but also effectively improve the response to ICIs in immunotherapy without obvious toxicity. It was also found to ameliorate the immunosuppressive tumor microenvironment and promote the antitumor immunity induced by ICIs by increasing CD8 tumor-infiltrating lymphocyte accumulation. Thus, TPE-IQ-2O PDT is a safe and effective antitumor therapy that can be combined with surgery or immunotherapy.
基于光动力疗法(PDT)的联合疗法因其强大的治疗效果而在各种癌症中受到广泛关注。在这里,我们旨在探索一种新型线粒体靶向光动力材料 TPE-IQ-2O 在联合疗法(联合手术或免疫疗法)中的安全性和有效性。通过细胞毒性评估和斑马鱼异种移植模型分别验证了 TPE-IQ-2O PDT 的安全性和有效性。在荷瘤小鼠中验证了 TPE-IQ-2O PDT 联合手术或免疫检查点抑制剂(ICIs)的有效性。小动物成像、免疫组织化学和流式细胞术用于确定潜在机制。TPE-IQ-2O PDT 不仅可以减少手术治疗中的肿瘤复发,而且可以有效提高免疫治疗中对 ICIs 的反应,而没有明显的毒性。还发现它可以通过增加 CD8 肿瘤浸润淋巴细胞的积累来改善免疫抑制性肿瘤微环境并促进 ICIs 诱导的抗肿瘤免疫。因此,TPE-IQ-2O PDT 是一种安全有效的抗肿瘤疗法,可以与手术或免疫疗法联合使用。