Journal Article

DKFZ-2022-02736

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Profiling the immune landscape in mucinous ovarian carcinoma.

Meagher, N. S. ; Hamilton, P. ; Milne, K. ; Thornton, S. ; Harris, B. ; Weir, A. ; Alsop, J. ; Bisinoto, C. ; Brenton, J. D. ; Brooks-Wilson, A. ; Chiu, D. S. ; Cushing-Haugen, K. L. ; Fereday, S. ; Garsed, D. W. ; Gayther, S. A. ; Gentry-Maharaj, A. ; Gilks, B. ; Jimenez-Linan, M. ; Kennedy, C. J. ; Le, N. D. ; Piskorz, A. M. ; Riggan, M. J. ; Shah, M. ; Singh, N. ; Talhouk, A. ; Widschwendter, M. ; Bowtell, D. D. L. ; Candido Dos Reis, F. J. ; Cook, L. S. ; Fortner, R. T.DKFZ* ; García, M. J. ; Harris, H. R. ; Huntsman, D. G. ; Karnezis, A. N. ; Köbel, M. ; Menon, U. ; Pharoah, P. D. P. ; Doherty, J. A. ; Anglesio, M. S. ; Pike, M. C. ; Pearce, C. L. ; Friedlander, M. L. ; DeFazio, A. ; Nelson, B. H. ; Ramus, S. J.

2022
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ygyno.2022.10.022

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.

Keyword(s): Immune infiltrate ; Mucinous ovarian carcinoma ; Rare histotype

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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