期刊
NANO LETTERS
卷 18, 期 11, 页码 7330-7342出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b03568
关键词
Tumor-associated macrophages; cancer immunotherapy; reactive oxygen species; photogeneration
类别
资金
- National Key Basic Research Program of China [2014CB744503]
- National Natural Science Foundation of China [81501533]
- Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health [ZIA EB000073]
- Scientific Research Foundation of the State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics [2016ZY002]
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.
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