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other·oncology, immunology, preclinical research, biomedical research·PMC10336067

Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy

Nature Communications · 12 authors, 4 centres

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TL;DR

Researchers developed a hydrogel microsphere vaccine designed to boost the immune response after tumor ablation therapy. In a mouse model of pancreatic cancer, the vaccine significantly improved survival and reduced the growth of distant metastases.

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This preclinical study designed a hydrogel microsphere vaccine containing FLT3L and CD40L to enhance antitumour immunity following irreversible electroporation (IRE) ablation. The vaccine was tested in an orthotopic pancreatic cancer model in male mice. The study reported that the vaccine promoted the migration of tumour-resident cDC1s to tumour-draining lymph nodes, initiating an antigen cross-presentation cascade that enhanced CD8+ T cell responses. This process was described as transforming the immunologically cold tumour microenvironment into a hot one. The central reported outcomes were significantly increased survival and inhibition of distant metastasis growth in the treated mice. Limitations acknowledged by the authors include the complex formulation for mass production and technical constraints in fully ruling out the role of other antigen-presenting cells.

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other

SPECIALTY

oncology

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ORIGINAL PAPER

PMC10336067

Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy

Nature Communications

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ABSTRACT

The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8 + T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.

CITATION EXPORT

Xiaoyu Liu, Yaping Zhuang, Wei Huang et al.. Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy. Nature Communications. (2023). https://doi.org/10.1038/s41467-023-39759-w

AUTHORS

12 · 4 CENTRES

Xiaoyu Liu, Yaping Zhuang, Wei Huang, Zhuozhuo Wu, Yingjie Chen, Qungang Shan, Yuefang Zhang, Zhiyuan Wu, Xiaoyi Ding, Zilong Qiu, Wenguo Cui, Zhongmin Wang

1grid.412277.50000 0004 1760 6738Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197, Ruijin 2nd Road, 200025 Shanghai, P. R. China
2grid.412277.50000 0004 1760 6738Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, 200025 Shanghai, P. R. China
3grid.507732.4Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, No.320 Yueyang Road, 200032 Shanghai, P. R. China
4grid.16821.3c0000 0004 0368 8293Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, No.149, South Chongqing Road, 200025 Shanghai, P. R. China