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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},
}