癌症研究
细胞毒性T细胞
磁热疗
钙网蛋白
转移
CD8型
免疫疗法
免疫系统
医学
封锁
癌症免疫疗法
免疫原性细胞死亡
免疫检查点
癌症
免疫学
化学
生物
材料科学
内科学
受体
细胞生物学
磁性纳米粒子
纳米技术
内质网
体外
纳米颗粒
生物化学
作者
Xiaoli Liu,Jianjun Zheng,Wei Sun,Xiao Zhao,Yao Li,Ningqiang Gong,Yanyun Wang,Xiaowei Ma,Tingbin Zhang,Lingyun Zhao,Yayi Hou,Zhibing Wu,Yang Du,Haiming Fan,Hui Hui,Xing‐Jie Liang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2019-07-22
卷期号:13 (8): 8811-8825
被引量:158
标识
DOI:10.1021/acsnano.9b01979
摘要
Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8+ cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8+ cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.
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