Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37130873.
- Also identified by DOI 10.1038/s41467-023-38245-7 and PMC identifier 10154421.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> 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.
Medical subject headings
- Female
- Mice
- Animals
- Sentinel Lymph Node
- Sentinel Lymph Node/pathology
- Sentinel Lymph Node Biopsy
- CD8-Positive T-Lymphocytes
- T-Lymphocytes, Cytotoxic
- Neoplasm Recurrence, Local
- Neoplasm Recurrence, Local/pathology
- Adjuvants, Immunologic
- Adjuvants, Immunologic/therapeutic use
- Lymph Nodes
- Lymph Nodes/pathology