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@ARTICLE{Gambichler:299784,
      author       = {T. Gambichler and S. Girke and N. Abu Rached and L. Susok
                      and J. Becker$^*$ and H.-J. Schulze and T. Hirsch and M.
                      Kückelhaus and S. Wellenbrock},
      title        = {{L}ow {I}ntratumoral {CD}200 {P}rotein {E}xpression in
                      {P}rimary {M}erkel {C}ell {C}arcinoma {I}s a {S}trong
                      {P}redictor for {D}isease {R}elapse.},
      journal      = {Cancers},
      volume       = {17},
      number       = {5},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2025-00539},
      pages        = {822},
      year         = {2025},
      abstract     = {Merkel cell carcinoma (MCC) is a rare and frequently fatal
                      form of skin cancer. Apart from Programmed Cell Death
                      Protein 1 (PD-1)/Programmed Death-Ligand 1 (PD-L1)
                      signaling, there is a lack of knowledge regarding other
                      immune checkpoint molecules. Recent studies have observed
                      elevated glycoprotein CD200 (also known as OX-2) mRNA
                      expression in in different types of tumors, with
                      CD200R-expressing myeloid cells present in the tumor
                      microenvironment. However, the potential role of the
                      CD200/CD200 axis as an additional checkpoint modulator
                      remains widely unexplored. The aim of this study was to
                      determine the intratumoral protein expression of CD200 as
                      well as CD200R in a larger cohort of MCC patients and to
                      correlate the expression levels with patients' outcomes.In
                      this multicenter study, we investigated 68 patients with MCC
                      (68 primary tumors and 15 corresponding metastases).
                      Immunohistochemistry (IHC) was performed for CD200 as well
                      as CD200R. Digital quantification and analysis of IHC were
                      performed using QuPath-0.2.3.CD200 and CD200R expression was
                      observed in $100\%$ of cases. Univariate analysis revealed
                      that low CD200 expression in primary tumors (p = 0.0007, HR
                      9.35), male sex (p = 0.045, HR 2.41), and immunosuppression
                      (p = 0.0031, HR 6.36) were significantly associated with MCC
                      relapse. Low CD200 expression was also linked to prior
                      immune checkpoint inhibitors (ICI) and/or chemotherapy
                      treatment (p = 0.037). Multivariable analysis confirmed that
                      low CD200 expression (p = 0.0012, HR 5.25) and
                      immunosuppression (p = 0.0056, HR 4.11) were independent
                      predictors of MCC relapse.Expression of CD200/CD200R
                      proteins is very high in MCC and may thus be of diagnostic
                      value. More importantly, low intratumoral CD200 protein
                      expression in primary MCC represents a robust independent
                      predictor of MCC relapse.},
      keywords     = {CD200/CC200R-signaling (Other) / Merkel cell carcinoma
                      (Other) / OX-2 (Other) / immune checkpoints (Other) /
                      immunotherapy (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:40075669},
      doi          = {10.3390/cancers17050822},
      url          = {https://inrepo02.dkfz.de/record/299784},
}