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@ARTICLE{Ma:289649,
author = {S. Ma and R. Sandhoff$^*$ and X. Luo and F. Shang$^*$ and
Q. Shi and Z. Li and J. Wu and Y. Ming and F. Schwarz$^*$
and A. A. M. Madi$^*$ and N. Weisshaar$^*$ and A. Mieg$^*$
and M. Hering$^*$ and F. Zettl$^*$ and X. Yan$^*$ and K.
Mohr$^*$ and N. ten Bosch$^*$ and Z. Li$^*$ and G. Poschet
and H.-R. Rodewald$^*$ and N. Papavasiliou$^*$ and X. Wang
and P. Gao and G. Cui$^*$},
title = {{S}erine enrichment in tumors promotes regulatory {T} cell
accumulation through sphinganine-mediated regulation of
c-{F}os.},
journal = {Science immunology},
volume = {9},
number = {94},
issn = {2470-9468},
address = {Washington, DC},
publisher = {AAAS},
reportid = {DKFZ-2024-00831},
pages = {eadg8817},
year = {2024},
note = {#EA:A411#LA:D192#},
abstract = {CD4+ regulatory T (Treg) cells accumulate in the tumor
microenvironment (TME) and suppress the immune system.
Whether and how metabolite availability in the TME
influences Treg cell differentiation is not understood.
Here, we measured 630 metabolites in the TME and found that
serine and palmitic acid, substrates required for the
synthesis of sphingolipids, were enriched. A serine-free
diet or a deficiency in Sptlc2, the rate-limiting enzyme
catalyzing sphingolipid synthesis, suppressed Treg cell
accumulation and inhibited tumor growth. Sphinganine, an
intermediate metabolite in sphingolipid synthesis,
physically interacted with the transcription factor c-Fos.
Sphinganine c-Fos interactions enhanced the genome-wide
recruitment of c-Fos to regions near the transcription start
sites of target genes including Pdcd1 (encoding PD-1), which
promoted Pdcd1 transcription and increased inducible Treg
cell differentiation in vitro in a PD-1-dependent manner.
Thus, Sptlc2-mediated sphingolipid synthesis translates the
extracellular information of metabolite availability into
nuclear signals for Treg cell differentiation and limits
antitumor immunity.},
cin = {A411 / D110 / W170 / D150 / D192 / F100 / D400},
ddc = {610},
cid = {I:(DE-He78)A411-20160331 / I:(DE-He78)D110-20160331 /
I:(DE-He78)W170-20160331 / I:(DE-He78)D150-20160331 /
I:(DE-He78)D192-20160331 / I:(DE-He78)F100-20160331 /
I:(DE-He78)D400-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38640251},
doi = {10.1126/sciimmunol.adg8817},
url = {https://inrepo02.dkfz.de/record/289649},
}