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Nano Research 2020, 13(6): 1509-1518 https://doi.org/10.1007/s12274-020-2737-5
Research Article | Issue | Published: 11 April 2020

Reverse immune suppressive microenvironment in tumor draining lymph nodes to enhance anti-PD1 immunotherapy via nanovaccine complexed microneedle

Show Author's Information Zhongzheng Zhou1,  Jianhui Pang1,  Xuanjin Wu1,  Wei Wu1,  Xiguang Chen1,2,  Ming Kong1( )
College of Marine Life Science, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
Qingdao National Laboratory for Marine Science and Technology, Wenhai Road, Qingdao 266237, China
Keywords:
transfersomes, microneedles, immunosuppressive microenvironment, tumor draining lymph node, αPD1
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Zhou Z, Pang J, Wu X, et al. Reverse immune suppressive microenvironment in tumor draining lymph nodes to enhance anti-PD1 immunotherapy via nanovaccine complexed microneedle. Nano Research, 2020, 13(6): 1509-1518. https://doi.org/10.1007/s12274-020-2737-5
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Abstract Full text Electronic supplementary material About this article

The maturation of dendritic cells (DCs) and infiltration effector T cells in tumor-draining lymph node (tdLN) and tumor tissue are crucial for immunotherapy. Despite constructive progresses have been made with anti-programmed death-1 (anti-PD1) checkpoint blockade for immunotherapy, the efficacy of PD1/PD-L1 therapy deserves to be improved. Here, we constructed a novel transfersomes based nanovaccine complexed microneedles to enhance anti-PD1 immunotherapy via transdermal immunization for skin tumor therapy. Transfersomes were functionalized with DCs targeting moiety αCD40, co-encapsulated with antigens and adjuvant poly I:C. Moreover, transdermal administration promoted accumulation in tumor-draining lymph nodes (tdLN), which could facilitate cellular uptake, activate DCs maturation and enhance Th1 immune responses. Using a mouse melanoma model, combined therapy of such nanovaccine complexed microneedles with pembrolizumab (αPD1) was able to enhance cytotoxic T lymphocytes activation, promote infiltration and reduce regulatory T cells frequency in tdLN and tumor tissues, which achieved reversion of the immunosuppressive microenvironment into immune activation. This study highlighted the potential of transfersomes based nanovaccines complexed microneedles as an attractive platform for tumor immunotherapy.


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Electronic supplementary material
About this article

Reverse immune suppressive microenvironment in tumor draining lymph nodes to enhance anti-PD1 immunotherapy via nanovaccine complexed microneedle

Show Author's information Zhongzheng Zhou1, Jianhui Pang1, Xuanjin Wu1, Wei Wu1, Xiguang Chen1,2, Ming Kong1( )
College of Marine Life Science, Ocean University of China, 5 Yushan Road, Qingdao 266003, China
Qingdao National Laboratory for Marine Science and Technology, Wenhai Road, Qingdao 266237, China

Abstract

The maturation of dendritic cells (DCs) and infiltration effector T cells in tumor-draining lymph node (tdLN) and tumor tissue are crucial for immunotherapy. Despite constructive progresses have been made with anti-programmed death-1 (anti-PD1) checkpoint blockade for immunotherapy, the efficacy of PD1/PD-L1 therapy deserves to be improved. Here, we constructed a novel transfersomes based nanovaccine complexed microneedles to enhance anti-PD1 immunotherapy via transdermal immunization for skin tumor therapy. Transfersomes were functionalized with DCs targeting moiety αCD40, co-encapsulated with antigens and adjuvant poly I:C. Moreover, transdermal administration promoted accumulation in tumor-draining lymph nodes (tdLN), which could facilitate cellular uptake, activate DCs maturation and enhance Th1 immune responses. Using a mouse melanoma model, combined therapy of such nanovaccine complexed microneedles with pembrolizumab (αPD1) was able to enhance cytotoxic T lymphocytes activation, promote infiltration and reduce regulatory T cells frequency in tdLN and tumor tissues, which achieved reversion of the immunosuppressive microenvironment into immune activation. This study highlighted the potential of transfersomes based nanovaccines complexed microneedles as an attractive platform for tumor immunotherapy.

Keywords: transfersomes, microneedles, immunosuppressive microenvironment, tumor draining lymph node, αPD1

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Publication history
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Acknowledgements

Publication history

Received: 23 December 2019
Revised: 26 February 2020
Accepted: 28 February 2020
Published: 11 April 2020
Issue date: June 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 31670972), and the Taishan Scholar Program, China.

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