Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis

Xin Guan, Liping Sun, Yuting Shen, Fengshan Jin, Xiaowan Bo, Chunyan Zhu, Xiaoxia Han, Xiaolong Li, Yu Chen (), Huixiong Xu () and Wenwen Yue ()
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Xin Guan: Tongji University
Liping Sun: Tongji University
Yuting Shen: Tongji University
Fengshan Jin: Tongji University
Xiaowan Bo: Tongji University
Chunyan Zhu: Tongji University
Xiaoxia Han: Tongji University
Xiaolong Li: Tongji University
Yu Chen: Shanghai University
Huixiong Xu: Tongji University
Wenwen Yue: Tongji University

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Cancer recurrence after surgical resection (SR) is a considerable challenge, and the biological effect of SR on the tumor microenvironment (TME) that is pivotal in determining postsurgical treatment efficacy remains poorly understood. Here, with an experimental model, we demonstrate that the genomic landscape shaped by SR creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells, fostering cancer progression and hindering PD-L1 blockade therapy. To address this issue, we engineer a radio-immunostimulant nanomedicine (IPI549@HMP) capable of targeting myeloid cells, and catalyzing endogenous H2O2 into O2 to achieve hypoxia-relieved radiotherapy (RT). The enhanced RT-mediated immunogenic effect results in postsurgical TME reprogramming and increased susceptibility to anti-PD-L1 therapy, which can suppress/eradicate locally residual and distant tumors, and elicits strong immune memory effects to resist tumor rechallenge. Our radioimmunotherapy points to a simple and effective therapeutic intervention against postsurgical cancer recurrence and metastasis.

Date: 2022
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DOI: 10.1038/s41467-022-30543-w

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