Myeloid cell-based delivery of IFN-γ reprograms the leukemia microenvironment and induces anti-tumoral immune responses.
Tie2-expressing monocytes
ex vivo gene therapy
immunotherapy
interferon-gamma
leukemia
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 10 2021
07 10 2021
Historique:
revised:
11
08
2021
received:
16
10
2020
accepted:
12
08
2021
pubmed:
31
8
2021
medline:
26
10
2021
entrez:
30
8
2021
Statut:
ppublish
Résumé
The immunosuppressive microenvironment surrounding tumor cells represents a key cause of treatment failure. Therefore, immunotherapies aimed at reprogramming the immune system have largely spread in the past years. We employed gene transfer into hematopoietic stem and progenitor cells to selectively express anti-tumoral cytokines in tumor-infiltrating monocytes/macrophages. We show that interferon-γ (IFN-γ) reduced tumor progression in mouse models of B-cell acute lymphoblastic leukemia (B-ALL) and colorectal carcinoma (MC38). Its activity depended on the immune system's capacity to respond to IFN-γ and drove the counter-selection of leukemia cells expressing surrogate antigens. Gene-based IFN-γ delivery induced antigen presentation in the myeloid compartment and on leukemia cells, leading to a wave of T cell recruitment and activation, with enhanced clonal expansion of cytotoxic CD8
Identifiants
pubmed: 34459560
doi: 10.15252/emmm.202013598
pmc: PMC8495462
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Interferon-gamma
82115-62-6
Banques de données
GEO
['GSE178941']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13598Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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