肿瘤微环境
癌症研究
免疫系统
细胞毒性T细胞
免疫疗法
癌症免疫疗法
免疫学
生物
生物化学
体外
作者
Yunkai Shang,Haipeng Lu,Li Liao,Suxin Li,Hui Xiong,Jing Yao
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-05-16
卷期号:17 (11): 10872-10887
被引量:11
标识
DOI:10.1021/acsnano.3c02657
摘要
Although cytotoxic treatments hold tremendous potential in boosting antitumor immunity, efferocytosis of tumor-associated macrophages (TAMs) could negatively remove apoptotic tumor cells through LC3-associated phagocytosis (LAP), resulting in inefficient tumor antigen presentation and immunosuppressive tumor microenvironment. To address this issue, we developed TAM-targeting nanospores (PC-CW) inspired by the predominant tropism of Rhizopus oryzae toward macrophages. To construct PC-CW, we disguised poly(sodium-p-styrenesulfonate) (PSS)-coated polyethylenimine (PEI)-shRNA nanocomplexes with the cell wall of R. oryzae conidia. LAP blockade by PC-CW delayed the degradation of engulfed tumor debris within TAMs, which not only enhanced antigen presentation but also initiated the domino effect of the antitumor immune response through STING signaling and TAM repolarization. Benefiting from this, PC-CW successfully sensitized the immune microenvironment and amplified CD8+ T cell responses following chemo-photothermal therapy, leading to substantial tumor growth control and metastasis prevention in tumor-bearing mouse models. The bioengineered nanospores represent a simple and versatile immunomodulatory strategy targeting TAMs for robust antitumor immunotherapy.
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