期刊
NANO LETTERS
卷 20, 期 1, 页码 242-251出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b03753
关键词
Cancer immunotherapy; checkpoint blockade; myeloid-derived suppressor cells (MDSCs); nanomedicines; neutrophils
类别
资金
- National Key R&D Program of China [2017YFA0205600]
- National Natural Science Foundation of China [51773191, 51633008, 51573176]
- Fundamental Research Funds for the Central Universities [WK3520000009, WK2090050042]
- Open Project of Key Laboratory of Biomedical Engineering of Guangdong Province [KLBEMGD201701]
Myeloid-derived suppressor cells (MDSCs) promote tumor immune escape through multiple mechanisms including suppressing antitumor activities of T lymphocytes. However, therapeutic abrogation of MDSCs often causes severe adverse effects, compensatory recruitment of alternative cell populations, and the multiplicity and complexity of relevant cytokines/receptors. Alternatively, suppressing the expansion and tumor trafficking of MDSCs may be a proficient and safe way for cancer treatment. Here we report that pseudoneutrophil cytokine sponges (pCSs) can disrupt expansion and tumor trafficking of MDSCs and reverse immune tolerance. Coated with plasma membranes of neutrophils phenotypically and morphologically similar to polymorphonuclear MDSCs (PMN-MDSCs), the nanosized pCSs inherited most membrane receptors from the parental neutrophils, enabling the neutralization of MDSC-related cytokines. Upon pCSs administration, the expansion of MDSCs and their enrichment in peripheral lymphoid organs and tumors were reduced without the compensatory influx of alternative myeloid subsets. In murine breast cancer and melanoma syngeneic models, pCSs treatment dramatically increased the number of tumor-infiltrating T lymphocytes and restored their antitumor functions. In addition, when pCSs were combined with the programmed cell death protein 1 (PD-1), the immune checkpoint blockade synergistically suppressed tumor progression and prolonged animal survival. Overall, the pseudocell nanoplatform opens up new paths toward effective cancer immunotherapy.
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