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@ARTICLE{Meagher:182555,
      author       = {N. S. Meagher and P. Hamilton and K. Milne and S. Thornton
                      and B. Harris and A. Weir and J. Alsop and C. Bisinoto and
                      J. D. Brenton and A. Brooks-Wilson and D. S. Chiu and K. L.
                      Cushing-Haugen and S. Fereday and D. W. Garsed and S. A.
                      Gayther and A. Gentry-Maharaj and B. Gilks and M.
                      Jimenez-Linan and C. J. Kennedy and N. D. Le and A. M.
                      Piskorz and M. J. Riggan and M. Shah and N. Singh and A.
                      Talhouk and M. Widschwendter and D. D. L. Bowtell and F. J.
                      Candido Dos Reis and L. S. Cook and R. T. Fortner$^*$ and M.
                      J. García and H. R. Harris and D. G. Huntsman and A. N.
                      Karnezis and M. Köbel and U. Menon and P. D. P. Pharoah and
                      J. A. Doherty and M. S. Anglesio and M. C. Pike and C. L.
                      Pearce and M. L. Friedlander and A. DeFazio and B. H. Nelson
                      and S. J. Ramus},
      title        = {{P}rofiling the immune landscape in mucinous ovarian
                      carcinoma.},
      journal      = {Gynecologic oncology},
      volume       = {168},
      issn         = {0090-8258},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2022-02736},
      pages        = {23 - 31},
      year         = {2022},
      abstract     = {Mucinous ovarian carcinoma (MOC) is a rare histotype of
                      ovarian cancer, with low response rates to standard
                      chemotherapy, and very poor survival for patients diagnosed
                      at advanced stage. There is a limited understanding of the
                      MOC immune landscape, and consequently whether immune
                      checkpoint inhibitors could be considered for a subset of
                      patients.We performed multicolor immunohistochemistry (IHC)
                      and immunofluorescence (IF) on tissue microarrays in a
                      cohort of 126 MOC patients. Cell densities were calculated
                      in the epithelial and stromal components for
                      tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T
                      cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells
                      (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells
                      (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared
                      these values with clinical factors. Univariate and
                      multivariable Cox Proportional Hazards assessed overall
                      survival. Unsupervised k-means clustering identified patient
                      subsets with common patterns of immune cell
                      infiltration.Mean densities of PD1+ cells, PD-L1-
                      macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were
                      higher in the stroma compared to the epithelium. Tumors from
                      advanced (Stage III/IV) MOC had greater epithelial
                      infiltration of PD-L1- macrophages, and fewer PD-L1+
                      macrophages compared with Stage I/II cancers (p = 0.004 and
                      p = 0.014 respectively). Patients with high epithelial
                      density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1-
                      macrophages, had poorer survival, and high epithelial CD79a
                      + plasma cells conferred better survival, all upon
                      univariate analysis only. Clustering showed that most MOC
                      $(86\%)$ had an immune depleted (cold) phenotype, with only
                      a small proportion $(11/76,14\%)$ considered immune inflamed
                      (hot) based on T cell and PD-L1 infiltrates.In summary, MOCs
                      are mostly immunogenically 'cold', suggesting they may have
                      limited response to current immunotherapies.},
      keywords     = {Immune infiltrate (Other) / Mucinous ovarian carcinoma
                      (Other) / Rare histotype (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36368129},
      doi          = {10.1016/j.ygyno.2022.10.022},
      url          = {https://inrepo02.dkfz.de/record/182555},
}