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@ARTICLE{AlsinaSanchis:182900,
      author       = {E. Alsina-Sanchis$^*$ and R. Mülfarth$^*$ and I. Moll$^*$
                      and S. V. Böhn$^*$ and L. Wiedmann$^*$ and L.
                      Jordana-Urriza$^*$ and T. Ziegelbauer$^*$ and E. Zimmer$^*$
                      and J. Taylor$^*$ and F. De Angelis Rigotti$^*$ and A.
                      Stögbauer$^*$ and B. D. Giaimo and A. Cerwenka and T.
                      Borggrefe and A. Fischer$^*$ and J. Rodriguez-Vita$^*$},
      title        = {{E}ndothelial {RBPJ} {I}s {E}ssential for the {E}ducation
                      of {T}umor-{A}ssociated {M}acrophages.},
      journal      = {Cancer research},
      volume       = {82},
      number       = {23},
      issn         = {0008-5472},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2022-03003},
      pages        = {4414 - 4428},
      year         = {2022},
      note         = {#EA:A270#LA:A270#},
      abstract     = {Epithelial ovarian cancer (EOC) is one of the most lethal
                      gynecologic cancers worldwide. EOC cells educate
                      tumor-associated macrophages (TAM) through CD44-mediated
                      cholesterol depletion to generate an immunosuppressive tumor
                      microenvironment (TME). In addition, tumor cells frequently
                      activate Notch1 receptors on endothelial cells (EC) to
                      facilitate metastasis. However, further work is required to
                      establish whether the endothelium also influences the
                      education of recruited monocytes. Here, we report that
                      canonical Notch signaling through RBPJ in ECs is an
                      important player in the education of TAMs and EOC
                      progression. Deletion of Rbpj in the endothelium of adult
                      mice reduced infiltration of monocyte-derived macrophages
                      into the TME of EOC and prevented the acquisition of a
                      typical TAM gene signature; this was associated with
                      stronger cytotoxic activity of T cells and decreased tumor
                      burden. Mechanistically, CXCL2 was identified as a novel
                      Notch/RBPJ target gene that regulated the expression of CD44
                      on monocytes and subsequent cholesterol depletion of TAMs.
                      Bioinformatic analysis of ovarian cancer patient data showed
                      that increased CXCL2 expression is accompanied by higher
                      expression of CD44 and TAM education. Together, these
                      findings indicate that EOC cells induce the tumor
                      endothelium to secrete CXCL2 to establish an
                      immunosuppressive microenvironment.Endothelial Notch
                      signaling favors immunosuppression by increasing CXCL2
                      secretion to stimulate CD44 expression in macrophages,
                      facilitating their education by tumor cells.},
      keywords     = {Humans / Female / Mice / Animals / Tumor-Associated
                      Macrophages / Endothelial Cells: pathology / Carcinoma,
                      Ovarian Epithelial: genetics / Ovarian Neoplasms: pathology
                      / Tumor Microenvironment / Endothelium: metabolism /
                      Cholesterol / Immunoglobulin J Recombination Signal
                      Sequence-Binding Protein: genetics / Cholesterol (NLM
                      Chemicals) / RBPJ protein, human (NLM Chemicals) /
                      Immunoglobulin J Recombination Signal Sequence-Binding
                      Protein (NLM Chemicals) / Rbpj protein, mouse (NLM
                      Chemicals)},
      cin          = {A270},
      ddc          = {610},
      cid          = {I:(DE-He78)A270-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36200806},
      doi          = {10.1158/0008-5472.CAN-22-0076},
      url          = {https://inrepo02.dkfz.de/record/182900},
}