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Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy

Author

Listed:
  • Bei Li

    (University of Macau
    University of Macau)

  • Guohao Wang

    (University of Macau
    University of Macau)

  • Kai Miao

    (University of Macau
    University of Macau)

  • Aiping Zhang

    (University of Macau
    University of Macau)

  • Liangyu Sun

    (University of Macau)

  • Xinwang Yu

    (University of Macau
    University of Macau)

  • Josh Haipeng Lei

    (University of Macau
    University of Macau)

  • Lisi Xie

    (University of Macau
    University of Macau)

  • Jie Yan

    (University of Macau
    University of Macau)

  • Wenxi Li

    (University of Macau
    University of Macau)

  • Chu-Xia Deng

    (University of Macau
    University of Macau)

  • Yunlu Dai

    (University of Macau
    University of Macau)

Abstract

Clinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.

Suggested Citation

  • Bei Li & Guohao Wang & Kai Miao & Aiping Zhang & Liangyu Sun & Xinwang Yu & Josh Haipeng Lei & Lisi Xie & Jie Yan & Wenxi Li & Chu-Xia Deng & Yunlu Dai, 2023. "Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38245-7
    DOI: 10.1038/s41467-023-38245-7
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    References listed on IDEAS

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    2. Yongliang Zhang & Joseph N. Blattman & Norman J. Kennedy & Julie Duong & Thang Nguyen & Ying Wang & Roger J. Davis & Philip D. Greenberg & Richard A. Flavell & Chen Dong, 2004. "Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5," Nature, Nature, vol. 430(7001), pages 793-797, August.
    3. Stefan Klein-Hessling & Khalid Muhammad & Matthias Klein & Tobias Pusch & Ronald Rudolf & Jessica Flöter & Musga Qureischi & Andreas Beilhack & Martin Vaeth & Carsten Kummerow & Christian Backes & Rou, 2017. "NFATc1 controls the cytotoxicity of CD8+ T cells," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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