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Nanoparticle accumulation in liver may induce resistance to immune checkpoint blockade therapy

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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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 32022043), the Suzhou Key Laboratory of Nanotechnology and Biomedicine, Collaborative Innovation Center of Suzhou Nano Science & Technology, the 111 Project, and Joint International Research Laboratory of Carbon-Based Functional Materials and Devices.

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  1. Huaxing Dai and Qianyu Yang contributed equally to this work.

Authors and Affiliations

  1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China

    Huaxing Dai, Qianyu Yang, Rong Sun, Yue Zhang, Qingle Ma, Yifan Shen, Beilei Wang, Yitong Chen, Jialu Xu, Bo Tian, Fang Xu & Chao Wang

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  1. Huaxing Dai
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Correspondence to Chao Wang.

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Dai, H., Yang, Q., Sun, R. et al. Nanoparticle accumulation in liver may induce resistance to immune checkpoint blockade therapy. Nano Res. 16, 5237–5246 (2023). https://doi.org/10.1007/s12274-022-5142-4

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  • DOI: https://doi.org/10.1007/s12274-022-5142-4

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