Reprogramming Tumor-Associated Macrophages by Nanoparticle-Based Reactive Oxygen Species Photogeneration
Reprogramming Tumor-Associated Macrophages by Nanoparticle-Based Reactive Oxygen Species Photogeneration
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DOI：
10.1021/acs.nanolett.8b03568
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发表时间：
2018-11-01
期刊：
影响因子：
10.8
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
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作者：
Shi, Changrong;Liu, Ting;Chen, Xiaoyuan
如果没有协调一致的策略来减轻肿瘤微环境的免疫抑制性质，癌症免疫治疗通常对已建立的肿瘤提供有限的临床益处。肿瘤相关巨噬细胞(TAMs)是免疫抑制肿瘤微环境的关键驱动力，免疫抑制微环境也促进肿瘤转移。在这里，我们成功地将TAMS重新编程为抗肿瘤M1表型，使用基于纳米颗粒的活性氧物种光生，证明了比内毒素刺激更高的效率和有效性。同时，通过抑制溶酶体质子泵和蛋白水解酶活性或促进肿瘤相关抗原在胞浆中的释放，TAMS的抗原提呈和T细胞启动作用得到加强。重新编程的TAMS协调细胞毒性淋巴细胞(CTL)在肿瘤中的募集，并引导记忆T细胞做出杀瘤反应。这一策略可以有效地根除肿瘤，抑制转移，并进一步防止肿瘤的复发，这为实现有效的癌症免疫治疗带来了巨大的希望。
Without coordinated strategies to mitigate the immunosuppressive nature of the tumor microenvironment, cancer immunotherapy generally offers limited clinical benefit for established tumors. Tumor-associated macrophages (TAMs) are the critical driver of this immunosuppressive tumor micro environment, which also promotes tumor metastasis. Here we successfully reprogrammed TAMs to an antitumor M1 phenotype using precision nanoparticle-based reactive oxygen species photogeneration, which demonstrated superior efficiency and efficacy over lipopolysaccharide stimulation. Meanwhile, antigen presentation and T-cell-priming by TAMs were enhanced by inhibiting lysosomal proton pump and proteolytic activity or by promoting tumor associated antigen release in the cytoplasm. The reprogrammed TAMs orchestrate cytotoxic lymphocyte (CTL) recruitment in the tumor and direct memory T-cells toward tumoricidal responses. This strategy could effectively eradicate tumors, inhibit metastasis, and further prevent their recurrence, which holds tremendous promise to realize potent cancer immunotherapy.