Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
04 11 2022
04 11 2022
Historique:
received:
31
08
2020
accepted:
12
10
2022
pubmed:
6
11
2022
medline:
9
11
2022
entrez:
5
11
2022
Statut:
epublish
Résumé
There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer.
Identifiants
pubmed: 36333531
doi: 10.1038/s42003-022-04102-4
pii: 10.1038/s42003-022-04102-4
pmc: PMC9636404
doi:
Substances chimiques
Siderophores
0
Ferrichrome
15630-64-5
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1181Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : SC1GM140982-01
Organisme : NIAID NIH HHS
ID : R01 AI137255
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA210192
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206069
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R01CA253329
Organisme : NCI NIH HHS
ID : R01 CA204552
Pays : United States
Informations de copyright
© 2022. The Author(s).
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