@article{Dai2023, 
author = {Huaxing Dai and Qianyu Yang and Rong Sun and Yue Zhang and Qingle Ma and Yifan Shen and Beilei Wang and Yitong Chen and Jialu Xu and Bo Tian and Fang Xu and Chao Wang},
title = {Nanoparticle accumulation in liver may induce resistance to immune checkpoint blockade therapy},
year = {2023},
journal = {Nano Research},
volume = {16},
number = {4},
pages = {5237-5246},
url = {https://www.sciopen.com/article/10.1007/s12274-022-5142-4},
doi = {10.1007/s12274-022-5142-4},
abstract = {Despite immune checkpoint blockade (ICB) therapy has transformed cancer treatment, only 20.2% of these patients achieved a response. Understanding resistance mechanisms to ICB is important for the treatment of a wider population. In this work, we occasionally found that the silica nanoparticles (SiO2 NPs) accumulated in the liver can induce resistance to following ICB therapy to a subcutaneous tumor in mice. By analysis of T cells frequency, we uncovered that SiO2 NPs in the liver resulted in a siphoning of T cells from circulation to the liver by produced chemokines. In addition, liver immunosuppressive cells further inhibit the function and induce apoptosis of recruited T cells, leading to a systemic loss and reduced tumor infiltration of T cells, which contributes to poor responses to ICB therapy. However, such effect is not observed in poly(lactic-co-glycolic acid) (PLGA) NPs treated mice under the same conditions, likely due to their much lower immunogenicity in perturbing the liver immune microenvironment, indicating that cancer is not a local disease but an ecosystem that is linked to the distal environment. We further provide a new mechanism insight into ICB resistance induced by liver accumulation of nanoparticles.}
}