肿瘤微环境
巨噬细胞极化
免疫疗法
免疫抑制
癌症研究
癌症免疫疗法
免疫系统
巨噬细胞
医学
微生物学
免疫学
化学
生物
体外
生物化学
作者
Baicheng Wei,Jingmei Pan,Ruiting Yuan,Binfen Shao,Yi Wang,Xing Guo,Shaobing Zhou
出处
期刊:Nano Letters
[American Chemical Society]
日期:2021-05-17
卷期号:21 (10): 4231-4240
被引量:171
标识
DOI:10.1021/acs.nanolett.1c00209
摘要
The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. The nanoparticles/bacteria complex (Ec-PR848) is fabricated for tumor targeting and TAM polarization, and PLGA-R848 (PR848) are attached to the surface of Escherichia coli (E. coli) MG1655 via electrostatic absorption. The toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and E. coli can greatly polarize M2 macrophages to M1 macrophages, while PDOX-induced ICD can also impair the immunosuppression of the tumor microenvironment. This strategy shows that tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapeutic drugs can commendably enhance the efficacy of immunotherapy.
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