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@ARTICLE{Sofia:294904,
      author       = {L.-R. Sofia$^*$ and Q.-F. Isaac$^*$ and I. Neta and S.
                      Soaad and F. Malik and S. Ruken$^*$ and B. Michele$^*$ and
                      C.-V. Sara$^*$ and M. Martin and V. Israel and A.
                      Cid-Arregui$^*$},
      title        = {{A}n integral membrane constitutively active heparanase
                      enhances the tumor infiltration capability of {NK} cells.},
      journal      = {OncoImmunology},
      volume       = {14},
      number       = {1},
      issn         = {2162-4011},
      address      = {Abingdon},
      publisher    = {Taylor $\&$ Franics},
      reportid     = {DKFZ-2024-02614},
      pages        = {2437917},
      year         = {2024},
      note         = {#EA:D122#LA:D122#},
      abstract     = {Eradication of cancer cells by the immune system requires
                      extravasation, infiltration and progression of immune cells
                      through the tumor extracellular matrix (ECM). These are also
                      critical determinants for successful adoptive cell
                      immunotherapy of solid tumors. Together with structural
                      proteins, such as collagens and fibronectin, heparan sulfate
                      (HS) proteoglycans are major components of the ECM.
                      Heparanase 1 (HPSE) is the only enzyme known to have
                      endoglycosidase activity that degrades HS. HPSE is expressed
                      at high levels in almost all hematopoietic cells, which
                      suggests that it plays a relevant role in immune cell
                      migration through solid tissues. Besides, tumor cells
                      express also HPSE as a way to facilitate tumor cell
                      resettlement and metastasis. Therefore, an increase in HPSE
                      in the tumor ECM would be detrimental. Here, we analyzed the
                      effects of constitutive expression of an active,
                      membrane-bound HPSE on the ability of human natural killer
                      (NK) cells to infiltrate tumors and eliminate tumor cells.
                      We demonstrate that NK cells expressing a chimeric active
                      form of HPSE on the cell surface as an integral membrane
                      protein, display significantly enhanced infiltration
                      capability into spheroids of various cancer cell lines, as
                      well as into xenograft tumors in immunodeficient mice. As a
                      result, tumor growth was significantly suppressed without
                      causing noticeable side effects. Altogether, our results
                      suggest that a constitutively expressed active HSPE on the
                      surface of immune effector cells enhances their capability
                      to access and eliminate tumor cells. This strategy opens new
                      possibilities for improving adoptive immune treatments using
                      NK cells.},
      keywords     = {Animals / Humans / Glucuronidase: metabolism /
                      Glucuronidase: genetics / Killer Cells, Natural: immunology
                      / Mice / Cell Line, Tumor / Mice, SCID / Cell Movement /
                      Neoplasms: immunology / Neoplasms: pathology / Neoplasms:
                      therapy / Mice, Inbred NOD / Xenograft Model Antitumor
                      Assays / Adoptive cell transfer (Other) / CAR (Other) / T
                      cell receptor (Other) / cell therapy (Other) / chimeric
                      antigen receptor (Other) / heparanase (Other) /
                      immunotherapy (Other) / natural killer (NK) cells (Other) /
                      heparanase (NLM Chemicals) / Glucuronidase (NLM Chemicals)},
      cin          = {D122},
      ddc          = {610},
      cid          = {I:(DE-He78)D122-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39651893},
      doi          = {10.1080/2162402X.2024.2437917},
      url          = {https://inrepo02.dkfz.de/record/294904},
}