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Nano Research 2022, 15(4): 3458-3470 https://doi.org/10.1007/s12274-021-3977-8
Research Article | Issue | Published: 26 December 2021

A “three musketeers” tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy

Show Author's Information Wenxi Li1,2,§,  Lisi Xie1,2,§,  Yi Ju3,  Zhan Zhang1,2,  Bei Li1,2,  Jie Li1,2,  Wei Sang1,2,  Guohao Wang1,2,  Hao Tian1,2,  Yunlu Dai1,2( )
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, China
MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau 999078, China
School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia

§ Wenxi Li and Lisi Xie contributed equally to this work.

Keywords:
interferon-γ (IFN-γ), anti-PD-L1 (aPD-L1), IDO-1 inhibitor (NLG919), neutralization, tumoricidal, positive anti-tumor feedback loop
Topics:
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Li W, Xie L, Ju Y, et al. A “three musketeers” tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy. Nano Research, 2022, 15(4): 3458-3470. https://doi.org/10.1007/s12274-021-3977-8
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Abstract Full text Electronic supplementary material About this article

Interferon-γ (IFN-γ), secreted by activated T cells predominantly, plays a crucial performance in the tumoricidal immune response. Unfortunately, a high level of IFN-γ severely ignites the immunosuppressive response, especially by increasing the expression of immune checkpoint programmed death-ligand 1 (PD-L1) and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO-1). Herein, we have explored a versatile IFN-γ-nano-integrator (aPD-L1-SH@Ce6@NLG919-PEG, simplified as CNDP) to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect. In this nano-integrator, photosensitizer chlorin e6 (Ce6) mediates photodynamic therapy (PDT) to re-shape immunogenicity and activate the adaptive immune response, followed by the secretion of high-level IFN-γ to struggle tumor cells. IDO-1 inhibitor (NLG919) afterwards mitigates the immunosuppressive behavior of IFN-γ by neutralizing the function of IDO-1. To turn “waste” into wealth, anti-PD-L1 (aPD-L1) antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade. Together, this “three musketeers” nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.


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Abstract
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Electronic supplementary material
About this article

A “three musketeers” tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy

Show Author's information Wenxi Li1,2,§, Lisi Xie1,2,§, Yi Ju3, Zhan Zhang1,2, Bei Li1,2, Jie Li1,2, Wei Sang1,2, Guohao Wang1,2, Hao Tian1,2, Yunlu Dai1,2( )
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, China
MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau 999078, China
School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria 3083, Australia

§ Wenxi Li and Lisi Xie contributed equally to this work.

Abstract

Interferon-γ (IFN-γ), secreted by activated T cells predominantly, plays a crucial performance in the tumoricidal immune response. Unfortunately, a high level of IFN-γ severely ignites the immunosuppressive response, especially by increasing the expression of immune checkpoint programmed death-ligand 1 (PD-L1) and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO-1). Herein, we have explored a versatile IFN-γ-nano-integrator (aPD-L1-SH@Ce6@NLG919-PEG, simplified as CNDP) to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect. In this nano-integrator, photosensitizer chlorin e6 (Ce6) mediates photodynamic therapy (PDT) to re-shape immunogenicity and activate the adaptive immune response, followed by the secretion of high-level IFN-γ to struggle tumor cells. IDO-1 inhibitor (NLG919) afterwards mitigates the immunosuppressive behavior of IFN-γ by neutralizing the function of IDO-1. To turn “waste” into wealth, anti-PD-L1 (aPD-L1) antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade. Together, this “three musketeers” nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.

Keywords: interferon-γ (IFN-γ), anti-PD-L1 (aPD-L1), IDO-1 inhibitor (NLG919), neutralization, tumoricidal, positive anti-tumor feedback loop

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Publication history
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Acknowledgements

Publication history

Received: 20 September 2021
Revised: 01 November 2021
Accepted: 02 November 2021
Published: 26 December 2021
Issue date: April 2022

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2021

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (Nos. 32171318 and 32101069), the Faculty of Health Sciences, University of Macau, the Start-up Research Grant (SRG) of University of Macau (No. SRG2018-00130-FHS), the Science and Technology Development Fund, Macau SAR (Nos. 0109/2018/A3, 0011/2019/AKP, 0113/2019/A2, and 0103/2021/A) and Shenzhen Science and Technology Innovation Commission, Shenzhen-Hong Kong-Macau Science and Technology Plan C (No. SGDX20201103093600004). We appreciate the assistance and support from the Proteomics, Metabolomics and Drug Development Core, Animal Research Core, and Biological Imaging and Stem Cell Core in the Faculty of Health Sciences, University of Macau.

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