Chemokine switch regulated by TGF-β1 in cancer-associated fibroblast subsets determines the efficacy of chemo-immunotherapy.
TGF-β
cancer
chemo-immunotherapy
chemokine
fibroblast
microenvironment
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2022
2022
Historique:
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
22
11
2022
Statut:
epublish
Résumé
Combining immunogenic cell death-inducing chemotherapies and PD-1 blockade can generate remarkable tumor responses. It is now well established that TGF-β1 signaling is a major component of treatment resistance and contributes to the cancer-related immunosuppressive microenvironment. However, whether TGF-β1 remains an obstacle to immune checkpoint inhibitor efficacy when immunotherapy is combined with chemotherapy is still to be determined. Several syngeneic murine models were used to investigate the role of TGF-β1 neutralization on the combinations of immunogenic chemotherapy (FOLFOX: 5-fluorouracil and oxaliplatin) and anti-PD-1. Cancer-associated fibroblasts (CAF) and immune cells were isolated from CT26 and PancOH7 tumor-bearing mice treated with FOLFOX, anti-PD-1 ± anti-TGF-β1 for bulk and single cell RNA sequencing and characterization. We showed that TGF-β1 neutralization promotes the therapeutic efficacy of FOLFOX and anti-PD-1 combination and induces the recruitment of antigen-specific CD8
Identifiants
pubmed: 36387055
doi: 10.1080/2162402X.2022.2144669
pii: 2144669
pmc: PMC9662195
doi:
Substances chimiques
Chemokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2144669Informations de copyright
© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
CB declares research grant from Roche, Bayer and advisory board for MSD, Sanofi, Bayer. All other authors report no conflict of interest.
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