% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Stachura:278581,
author = {P. Stachura and W. Liu and H. C. Xu and A. Wlodarczyk and
O. Stencel and P. Pandey and M. Vogt and S. Bhatia and D.
Picard$^*$ and M. Remke$^*$ and K. S. Lang and D.
Häussinger and B. Homey and P. A. Lang and A. Borkhardt and
A. A. Pandyra},
title = {{U}nleashing {T} cell anti-tumor immunity: new potential
for 5-{N}onloxytryptamine as an agent mediating {MHC}-{I}
upregulation in tumors.},
journal = {Molecular cancer},
volume = {22},
number = {1},
issn = {1476-4598},
address = {London},
publisher = {Biomed Central},
reportid = {DKFZ-2023-01662},
pages = {136},
year = {2023},
abstract = {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+ T cells. 5-NL's pro-immune effects
were not directly consequential to T cells. Rather, 5-NL
upregulated antigen presenting machinery in melanoma and
other tumor cells in vitro and in vivo without increasing
PD-L1 expression. Mechanistic studies indicated that 5-NL's
induced MHC-I expression was inhibited by pharmacologically
preventing cAMP Response Element-Binding Protein (CREB)
phosphorylation. Importantly, 5-NL combined with anti-PD1
therapy showed significant improvement when compared to
single anti-PD-1 treatment.This study demonstrates novel
therapeutic opportunities for augmenting immune responses in
poorly immunogenic tumors.},
keywords = {5-Nonyloxytryptamine (5-NL) (Other) / Antigen-presenting
machinery (Other) / CD8+ T cells (Other) / Cold tumors
(Other) / Immunotherapy (Other) / cAMP response
element-binding protein (CREB) (Other)},
cin = {ED01},
ddc = {570},
cid = {I:(DE-He78)ED01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37582744},
doi = {10.1186/s12943-023-01833-8},
url = {https://inrepo02.dkfz.de/record/278581},
}