2. Academic Validation
  3. Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis

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

  • Nat Commun. 2022 May 20;13(1):2834. doi: 10.1038/s41467-022-30543-w.
Xin Guan  # 1 2 3,  Liping Sun  # 1 2 3,  Yuting Shen  # 1 2 3,  Fengshan Jin 1 2 3,  Xiaowan Bo 1 2 3,  Chunyan Zhu 1 2 3,  Xiaoxia Han 1 2 3,  Xiaolong Li 1 2 3,  Yu Chen 4,  Huixiong Xu 5 6 7 8,  Wenwen Yue 9 10 11
Affiliations

Affiliations

  • 1 Department of Medical Ultrasound and Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, P.R. China.
  • 2 Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, School of Medicine, Tongji University, Shanghai, 200072, P.R. China.
  • 3 Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment; National Clinical Research Center for Interventional Medicine, Shanghai, 200072, P. R. China.
  • 4 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China. [email protected].
  • 5 Department of Medical Ultrasound and Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, P.R. China. [email protected].
  • 6 Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, School of Medicine, Tongji University, Shanghai, 200072, P.R. China. [email protected].
  • 7 Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment; National Clinical Research Center for Interventional Medicine, Shanghai, 200072, P. R. China. [email protected].
  • 8 Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China. [email protected].
  • 9 Department of Medical Ultrasound and Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, P.R. China. [email protected].
  • 10 Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, School of Medicine, Tongji University, Shanghai, 200072, P.R. China. [email protected].
  • 11 Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment; National Clinical Research Center for Interventional Medicine, Shanghai, 200072, P. R. China. [email protected].
  • # Contributed equally.
PMID: 35595770 DOI: 10.1038/s41467-022-30543-w
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.

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