Nanocarrier-based activation of necroptotic cell death potentiates cancer immunotherapy
Nanocarrier-based activation of necroptotic cell death potentiates cancer immunotherapy
复制标题
基于纳米载体的坏死性细胞死亡激活增强了癌症免疫治疗
DOI：
10.1039/d0nr05832g
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发表时间：
2021
期刊：
影响因子：
6.7
通讯作者：
Zhou Pang-Hu
中科院分区：
文献类型：
--
作者：
Xia Gan-Qing;Lei Tian-Run;Yu Teng-Bo;Zhou Pang-Hu
尽管免疫检查点抑制剂在临床实践中已显示出有效的抗肿瘤作用，但大多数肿瘤的低免疫原性仍导致较低的应答率和对单一免疫疗法的较高抗性。最近的研究表明，免疫原性细胞死亡（ICD）增强了针对某些癌症的T细胞应答，因此表明这种联合治疗可能进一步提高抗PD-1/PD-L1产生的抗肿瘤免疫力。本文报道了一种稳健的协同策略，以整合坏死性细胞死亡的激活和随后使用免疫检查点抑制剂。脂质体具有良好的生物相容性，被广泛用作药物载体。使用脂质体作为负载TNF-α的纳米平台实现了体内肿瘤靶向和在肿瘤微环境中的长期保留。TNF-α脂质体处理的肿瘤细胞表现出ICD的特征，包括高迁移率族蛋白1（HMGB 1）和乳酸脱氢酶（LDH）的释放。此外，TNF-α引起的肿瘤细胞坏死诱导肿瘤特异性抗原的原位释放，从而在与检查点阻断疗法组合时增加树突状细胞（DC）活化和T细胞浸润。总的来说，这种协同策略可显著减少肿瘤，其中TNF-α负载的脂质体将肿瘤细胞转化为内源性疫苗并提高抗PD-1/PD-L1的抗肿瘤免疫力。
Even though immunological checkpoint inhibitors have demonstrated a potent anti-tumor effect in clinical practice, the low immunogenicity of the majority of tumors still results in a lower response rate and a higher resistance to mono-immunotherapy. Recent studies revealed that immunogenic cell death (ICD) augments T cell responses against some cancers, thus indicating that this combination therapy may further improve the anti-tumor immunity produced by anti-PD-1/PD-L1. Herein a robust synergetic strategy is reported to integrate the activation of necroptotic cell death and the subsequent using of immune checkpoint inhibitors. Liposomes have good biocompatibility and are widely used as drug carriers. Using liposomes as TNF-α-loaded nanoplatforms achieves in vivo tumor targeting and long-term retention in the tumor microenvironment. Tumor cells treated with TNF-α-loaded liposomes exhibited the hallmarks of ICD including the release of high mobility group box 1 (HMGB1) and lactate dehydrogenase (LDH). Additionally, the tumor cell necrosis caused by TNF-α induces the in situ release of tumor-specific antigens, thus increasing the dendritic cell (DC) activation and T cell infiltration when combined with the checkpoint blockade therapy. Collectively, significant tumor reduction is accomplishable by this synergetic strategy, in which TNF-α-loaded liposomes convert the tumor cell into an endogenous vaccine and improve the anti-tumor immunity of anti-PD-1/PD-L1.