In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases.
Colorectal cancer (CRC)
EOMES
Gene therapy
Immunotherapy
Interferon-alpha
Interleukin-10 (IL-10)
Liver metastases
Pancreatic cancer
Tumor-associated macrophages (TAMs)
Type 1 regulatory T cells (Tr1)
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
13 11 2023
13 11 2023
Historique:
received:
17
02
2023
revised:
27
07
2023
accepted:
27
09
2023
medline:
16
11
2023
pubmed:
21
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Liver metastases are associated with poor response to current pharmacological treatments, including immunotherapy. We describe a lentiviral vector (LV) platform to selectively engineer liver macrophages, including Kupffer cells and tumor-associated macrophages (TAMs), to deliver type I interferon (IFNα) to liver metastases. Gene-based IFNα delivery delays the growth of colorectal and pancreatic ductal adenocarcinoma liver metastases in mice. Response to IFNα is associated with TAM immune activation, enhanced MHC-II-restricted antigen presentation and reduced exhaustion of CD8
Identifiants
pubmed: 37863068
pii: S1535-6108(23)00347-1
doi: 10.1016/j.ccell.2023.09.014
pii:
doi:
Substances chimiques
CTLA-4 Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1892-1910.e10Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests L.N., M.L.S., and T.K. are inventors on a patent on KC-directed gene transfer and L.N. is an inventor on patents on miRNA-regulated LV technology filed and managed by the San Raffaele Scientific Institute and the Telethon Foundation.