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; Yunlu Dai

doi:10.1038/s41467-023-38245-7

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

Nat Commun. 2023 May 2;14(1):2518. doi: 10.1038/s41467-023-38245-7.

Authors

Bei Li^#^{1

2}, Guohao Wang^#^{1

2}, Kai Miao^#^{1

2}, Aiping Zhang^{1

2}, Liangyu Sun¹, Xinwang Yu^{1

2}, Josh Haipeng Lei^{1

2}, Lisi Xie^{1

2}, Jie Yan^{1

2}, Wenxi Li^{1

2}, Chu-Xia Deng^{3

4}, Yunlu Dai^{5

6}

Affiliations

¹ Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
² MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China.
³ Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China. cxdeng@um.edu.mo.
⁴ MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China. cxdeng@um.edu.mo.
⁵ Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China. yldai@um.edu.mo.
⁶ MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China. yldai@um.edu.mo.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / therapeutic use
Animals
CD8-Positive T-Lymphocytes
Female
Lymph Nodes / pathology
Mice
Neoplasm Recurrence, Local / pathology
Sentinel Lymph Node Biopsy
Sentinel Lymph Node* / pathology
T-Lymphocytes, Cytotoxic

Substances

Adjuvants, Immunologic