Zhou Yuhan, Ye Ting, Ye Chengzhi, Wan Chao, Yuan Siyue, Liu Yushuai, Li Tianyu, Jiang Fagang, Lovell Jonathan F, Jin Honglin, Chen Jing
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, PR China.
Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
Bioact Mater. 2021 Jul 24;9:541-553. doi: 10.1016/j.bioactmat.2021.07.019. eCollection 2022 Mar.
Autologous tumor cells and cell-derived secretions (CDS) can induce antitumor immune responses. The conditions in which cells are cultured and treated impact CDS, and cellular insults alter their composition and function. In this study, we generated CDS from tumor cells exposed to normal culture conditions, hypoxia, cisplatin, radiotherapy, photodynamic therapy, or hypochlorous acid (HOCl). HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia, cisplatin, radiotherapy or photodynamic therapy. To improve HOCl-CDS activity at the tumor site, we loaded HOCl-CDS into a melittin-encapsulated hydrogel scaffold. When injected intratumorally, the HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration, and tumor-associated macrophage reprogramming towards an M1 phenotype. The hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 melanoma. Furthermore, hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint blockade. These results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.
自体肿瘤细胞和细胞衍生分泌物（CDS）可诱导抗肿瘤免疫反应。细胞培养和处理的条件会影响CDS，而细胞损伤会改变其组成和功能。在本研究中，我们从暴露于正常培养条件、缺氧、顺铂、放疗、光动力疗法或次氯酸（HOCl）的肿瘤细胞中生成了CDS。与缺氧、顺铂、放疗或光动力疗法生成的CDS相比，HOCl-CDS对树突状细胞和巨噬细胞显示出最强的刺激作用。为了提高HOCl-CDS在肿瘤部位的活性，我们将HOCl-CDS加载到蜂毒肽包裹的水凝胶支架中。当瘤内注射时，HOCl-CDS水凝胶促进肿瘤细胞死亡、细胞毒性T淋巴细胞浸润以及肿瘤相关巨噬细胞重编程为M1表型。该水凝胶抑制肿瘤生长并延长携带B16-F10黑色素瘤小鼠的生存期。此外，水凝胶递送的HOCl-CDS增强了免疫检查点阻断的抗肿瘤作用。这些结果强调了CDS生成方法和递送方式对改善癌症免疫治疗的重要性。
