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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},
}