Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy.
Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy.
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蜂毒肽水凝胶中传递的次氯酸处理的肿瘤细胞的分泌物可增强癌症免疫疗法
DOI：
10.1016/j.bioactmat.2021.07.019
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhou Y;Ye T;Ye C;Wan C;Yuan S;Liu Y;Li T;Jiang F;Lovell JF;Jin H;Chen J
自体肿瘤细胞及其分泌物（CDS）可诱导抗肿瘤免疫反应。细胞培养和处理的条件影响CDS，细胞损伤改变其组成和功能。在这项研究中，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）的肿瘤细胞中产生CDS。在体外HOCl-CDS表现出最强的刺激作用的树突状细胞和巨噬细胞相比，CDS产生缺氧，顺铂，放疗或光动力疗法。为了提高HOCl-CDS在肿瘤部位的活性，我们将HOCl-CDS装载到蜂毒肽包封的水凝胶支架中。当瘤内注射时，HOCl-CDS水凝胶促进肿瘤细胞死亡、细胞毒性T淋巴细胞浸润和肿瘤相关巨噬细胞向M1表型重编程。这种水凝胶抑制了肿瘤的生长，并延长了携带B16-F10黑色素瘤的小鼠的存活时间。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生成方法和递送方法对于改善癌症免疫疗法的重要性。方案1.用于产生用于增强的癌症免疫疗法的HOCl-CDS和HOCl-CDS水凝胶的示意图。HOCl处理的肿瘤细胞来源的分泌物（HOCl-CDS）是树突状细胞和巨噬细胞上的强免疫刺激剂。通过将HOCl-CDS负载到蜂毒肽包封的水凝胶支架中来开发多功能HOCl-CDS水凝胶。HOCl-CDS水凝胶促进小鼠肿瘤细胞死亡、细胞毒性T淋巴细胞浸润和M1-TAM极化。HOCl-CDS水凝胶协同增强了抗PD-1的治疗效果，并进一步增强了癌症免疫治疗。
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). In vitro 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. Scheme 1. Schematic diagram for generating the HOCl-CDS and HOCl-CDS hydrogel for potentiated cancer immunotherapy. HOCl-treated tumor cell-derived secretions (HOCl-CDS) is a robust immune-stimulator on dendritic cells and macrophages. A multifunctional HOCl-CDS hydrogel was developed by loading HOCl-CDS into a melittin-encapsulated hydrogel scaffold. HOCl-CDS hydrogel promoted tumor cell death, cytotoxic T lymphocyte infiltration and M1-TAM polarization in mice. HOCl-CDS hydrogel synergistically augmented the therapeutic effect of anti-PD-1 and further potentiated cancer immunotherapy.
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