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

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.