Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors.
5-Nonyloxytryptamine (5-NL)
Antigen-presenting machinery
CD8+ T cells
Cold tumors
Immunotherapy
cAMP response element-binding protein (CREB)
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
15 08 2023
15 08 2023
Historique:
received:
05
10
2022
accepted:
27
07
2023
medline:
17
8
2023
pubmed:
16
8
2023
entrez:
15
8
2023
Statut:
epublish
Résumé
New therapies are urgently needed in melanoma, particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. To uncover novel potentiators of T cell anti-tumor immunity, we carried out an ex vivo pharmacological screen and identified 5-Nonyloxytryptamine (5-NL), a serotonin agonist, as increasing the ability of T cells to target tumor cells. The pharmacological screen utilized lymphocytic choriomeningitis virus (LCMV)-primed splenic T cells and melanoma B16.F10 cells expressing the LCMV gp33 CTL epitope. In vivo tumor growth in C57BL/6 J and NSG mice, in vivo antibody depletion, flow cytometry, immunoblot, CRISPR/Cas9 knockout, histological and RNA-Seq analyses were used to decipher 5-NL's immunomodulatory effects in vitro and in vivo. 5-NL delayed tumor growth in vivo and the phenotype was dependent on the hosts' immune system, specifically CD8 This study demonstrates novel therapeutic opportunities for augmenting immune responses in poorly immunogenic tumors.
Sections du résumé
BACKGROUND
New therapies are urgently needed in melanoma, particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. To uncover novel potentiators of T cell anti-tumor immunity, we carried out an ex vivo pharmacological screen and identified 5-Nonyloxytryptamine (5-NL), a serotonin agonist, as increasing the ability of T cells to target tumor cells.
METHODS
The pharmacological screen utilized lymphocytic choriomeningitis virus (LCMV)-primed splenic T cells and melanoma B16.F10 cells expressing the LCMV gp33 CTL epitope. In vivo tumor growth in C57BL/6 J and NSG mice, in vivo antibody depletion, flow cytometry, immunoblot, CRISPR/Cas9 knockout, histological and RNA-Seq analyses were used to decipher 5-NL's immunomodulatory effects in vitro and in vivo.
RESULTS
5-NL delayed tumor growth in vivo and the phenotype was dependent on the hosts' immune system, specifically CD8
CONCLUSIONS
This study demonstrates novel therapeutic opportunities for augmenting immune responses in poorly immunogenic tumors.
Identifiants
pubmed: 37582744
doi: 10.1186/s12943-023-01833-8
pii: 10.1186/s12943-023-01833-8
pmc: PMC10426104
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
136Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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