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| 001 | 182555 | ||
| 005 | 20240229145722.0 | ||
| 024 | 7 | _ | |a 10.1016/j.ygyno.2022.10.022 |2 doi |
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| 024 | 7 | _ | |a 1095-6859 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2022-02736 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Meagher, Nicola S |b 0 |
| 245 | _ | _ | |a Profiling the immune landscape in mucinous ovarian carcinoma. |
| 260 | _ | _ | |a Amsterdam [u.a.] |c 2022 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1668427471_7316 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
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| 650 | _ | 7 | |a Immune infiltrate |2 Other |
| 650 | _ | 7 | |a Mucinous ovarian carcinoma |2 Other |
| 650 | _ | 7 | |a Rare histotype |2 Other |
| 700 | 1 | _ | |a Hamilton, Phineas |b 1 |
| 700 | 1 | _ | |a Milne, Katy |b 2 |
| 700 | 1 | _ | |a Thornton, Shelby |b 3 |
| 700 | 1 | _ | |a Harris, Bronwyn |b 4 |
| 700 | 1 | _ | |a Weir, Ashley |b 5 |
| 700 | 1 | _ | |a Alsop, Jennifer |b 6 |
| 700 | 1 | _ | |a Bisinoto, Christiani |b 7 |
| 700 | 1 | _ | |a Brenton, James D |b 8 |
| 700 | 1 | _ | |a Brooks-Wilson, Angela |b 9 |
| 700 | 1 | _ | |a Chiu, Derek S |b 10 |
| 700 | 1 | _ | |a Cushing-Haugen, Kara L |b 11 |
| 700 | 1 | _ | |a Fereday, Sian |b 12 |
| 700 | 1 | _ | |a Garsed, Dale W |b 13 |
| 700 | 1 | _ | |a Gayther, Simon A |b 14 |
| 700 | 1 | _ | |a Gentry-Maharaj, Aleksandra |b 15 |
| 700 | 1 | _ | |a Gilks, Blake |b 16 |
| 700 | 1 | _ | |a Jimenez-Linan, Mercedes |b 17 |
| 700 | 1 | _ | |a Kennedy, Catherine J |b 18 |
| 700 | 1 | _ | |a Le, Nhu D |b 19 |
| 700 | 1 | _ | |a Piskorz, Anna M |b 20 |
| 700 | 1 | _ | |a Riggan, Marjorie J |b 21 |
| 700 | 1 | _ | |a Shah, Mitul |b 22 |
| 700 | 1 | _ | |a Singh, Naveena |b 23 |
| 700 | 1 | _ | |a Talhouk, Aline |b 24 |
| 700 | 1 | _ | |a Widschwendter, Martin |b 25 |
| 700 | 1 | _ | |a Bowtell, David D L |b 26 |
| 700 | 1 | _ | |a Candido Dos Reis, Francisco J |b 27 |
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| 700 | 1 | _ | |a García, María J |b 30 |
| 700 | 1 | _ | |a Harris, Holly R |b 31 |
| 700 | 1 | _ | |a Huntsman, David G |b 32 |
| 700 | 1 | _ | |a Karnezis, Anthony N |b 33 |
| 700 | 1 | _ | |a Köbel, Martin |b 34 |
| 700 | 1 | _ | |a Menon, Usha |b 35 |
| 700 | 1 | _ | |a Pharoah, Paul D P |b 36 |
| 700 | 1 | _ | |a Doherty, Jennifer A |b 37 |
| 700 | 1 | _ | |a Anglesio, Michael S |b 38 |
| 700 | 1 | _ | |a Pike, Malcolm C |b 39 |
| 700 | 1 | _ | |a Pearce, Celeste Leigh |b 40 |
| 700 | 1 | _ | |a Friedlander, Michael L |b 41 |
| 700 | 1 | _ | |a DeFazio, Anna |b 42 |
| 700 | 1 | _ | |a Nelson, Brad H |b 43 |
| 700 | 1 | _ | |a Ramus, Susan J |b 44 |
| 773 | _ | _ | |a 10.1016/j.ygyno.2022.10.022 |g Vol. 168, p. 23 - 31 |0 PERI:(DE-600)1467974-7 |p 23 - 31 |t Gynecologic oncology |v 168 |y 2022 |x 0090-8258 |
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