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@ARTICLE{Lopez:282878,
      author       = {V. Lopez and H. J. M. Schuh and S. Mirza and V. J. Vaaßen
                      and M. S. Schmidt and K. Sylvester and R. M. Idris and C.
                      Renn and L. Schäkel and J. Pelletier and J. Sévigny and A.
                      Naggi and B. Scheffler$^*$ and S.-Y. Lee and G. Bendas and
                      C. E. Müller},
      title        = {{H}eparins are potent inhibitors of ectonucleotide
                      pyrophosphatase/phospho-diesterase-1 ({NPP}1) - a promising
                      target for the immunotherapy of cancer.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2023-01880},
      pages        = {1173634},
      year         = {2023},
      abstract     = {Heparins, naturally occurring glycosaminoglycans, are
                      widely used for thrombosis prevention. Upon application as
                      anticoagulants in cancer patients, heparins were found to
                      possess additional antitumor activities. Ectonucleotidases
                      have recently been proposed as novel targets for cancer
                      immunotherapy.In the present study, we discovered that
                      heparin and its derivatives act as potent, selective,
                      allosteric inhibitors of the poorly investigated
                      ectonucleotidase NPP1 (nucleotide
                      pyrophosphatase/phosphodiesterase-1, CD203a).
                      Structure-activity relationships indicated that NPP1
                      inhibition could be separated from the compounds'
                      antithrombotic effect. Moreover, unfractionated heparin
                      (UFH) and different low molecular weight heparins (LMWHs)
                      inhibited extracellular adenosine production by the
                      NPP1-expressing glioma cell line U87 at therapeutically
                      relevant concentrations. As a consequence, heparins
                      inhibited the ability of U87 cell supernatants to induce
                      CD4+ T cell differentiation into immunosuppressive Treg
                      cells.NPP1 inhibition likely contributes to the anti-cancer
                      effects of heparins, and their specific optimization may
                      lead to improved therapeutics for the immunotherapy of
                      cancer.},
      keywords     = {NPP1 (Other) / U87 glioblastoma cells (Other) / adenosine
                      (Other) / ectonucleotidase inhibitors (Other) / heparin
                      (Other) / immuno-oncology (Other)},
      cin          = {ED01},
      ddc          = {610},
      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:37711611},
      pmc          = {pmc:PMC10497752},
      doi          = {10.3389/fimmu.2023.1173634},
      url          = {https://inrepo02.dkfz.de/record/282878},
}