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@ARTICLE{Arseni:212428,
      author       = {L. Arseni$^*$ and R. Sharma$^*$ and N. Mack$^*$ and D.
                      Nagalla$^*$ and S. Ohl$^*$ and T. Hielscher$^*$ and M.
                      Singhal$^*$ and R. Engel$^*$ and H. Augustin$^*$ and R.
                      Sandhoff$^*$ and C. Herold-Mende and B. Tews$^*$ and P.
                      Lichter$^*$ and M. Seiffert$^*$},
      title        = {{S}phingosine-1-{P}hosphate {R}ecruits {M}acrophages and
                      {M}icroglia and {I}nduces a {P}ro-{T}umorigenic {P}henotype
                      {T}hat {F}avors {G}lioma {P}rogression.},
      journal      = {Cancers},
      volume       = {15},
      number       = {2},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-00147},
      pages        = {479},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance / #EA:B060#LA:B060#},
      abstract     = {Glioblastoma is the most aggressive brain tumor in adults.
                      Treatment failure is predominantly caused by its high
                      invasiveness and its ability to induce a supportive
                      microenvironment. As part of this, a major role for
                      tumor-associated macrophages/microglia (TAMs) in
                      glioblastoma development was recognized. Phospholipids are
                      important players in various fundamental biological
                      processes, including tumor-stroma crosstalk, and the
                      bioactive lipid sphingosine-1-phosphate (S1P) has been
                      linked to glioblastoma cell proliferation, invasion, and
                      survival. Despite the urgent need for better therapeutic
                      approaches, novel strategies targeting sphingolipids in
                      glioblastoma are still poorly explored. Here, we showed that
                      higher amounts of S1P secreted by glioma cells are
                      responsible for an active recruitment of TAMs, mediated by
                      S1P receptor (S1PR) signaling through the modulation of
                      Rac1/RhoA. This resulted in increased infiltration of TAMs
                      in the tumor, which, in turn, triggered their
                      pro-tumorigenic phenotype through the inhibition of
                      NFkB-mediated inflammation. Gene set enrichment analyses
                      showed that such an anti-inflammatory microenvironment
                      correlated with shorter survival of glioblastoma patients.
                      Inhibition of S1P restored a pro-inflammatory phenotype in
                      TAMs and resulted in increased survival of tumor-bearing
                      mice. Taken together, our results establish a crucial role
                      for S1P in fine-tuning the crosstalk between glioma and
                      infiltrating TAMs, thus pointing to the S1P-S1PR axis as an
                      attractive target for glioma treatment.},
      keywords     = {S1P (Other) / anti-inflammatory (Other) / glioblastoma
                      (Other) / microenvironment (Other) / tumor-associated
                      macrophages/microglia (Other)},
      cin          = {B060 / B062 / C060 / A190 / A411},
      ddc          = {610},
      cid          = {I:(DE-He78)B060-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)A190-20160331 /
                      I:(DE-He78)A411-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36672428},
      pmc          = {pmc:PMC9856301},
      doi          = {10.3390/cancers15020479},
      url          = {https://inrepo02.dkfz.de/record/212428},
}