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

Bei Li, Guohao Wang, Kai Miao, Aiping Zhang, Liangyu Sun, Xinwang Yu, Josh Haipeng Lei, Lisi Xie, Jie Yan, Wenxi Li, Chu-Xia Deng () and Yunlu Dai ()
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Bei Li: University of Macau
Guohao Wang: University of Macau
Kai Miao: University of Macau
Aiping Zhang: University of Macau
Liangyu Sun: University of Macau
Xinwang Yu: University of Macau
Josh Haipeng Lei: University of Macau
Lisi Xie: University of Macau
Jie Yan: University of Macau
Wenxi Li: University of Macau
Chu-Xia Deng: University of Macau
Yunlu Dai: University of Macau

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38245-7

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