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oai:repisalud.isciii.es:20.500.12105/265272025-12-18T12:55:43Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Meagher, Nicola S author Hamilton, Phineas author Milne, Katy author Thornton, Shelby author Harris, Bronwyn author Weir, Ashley author Alsop, Jennifer author Bisinoto, Christiani author Brenton, James D author Brooks-Wilson, Angela author Chiu, Derek S author Cushing-Haugen, Kara L author Fereday, Sian author Garsed, Dale W author Gayther, Simon A author Gentry-Maharaj, Aleksandra author Gilks, Blake author Jimenez-Linan, Mercedes author Kennedy, Catherine J author Le, Nhu D author Piskorz, Anna M author Riggan, Marjorie J author Shah, Mitul author Singh, Naveena author Talhouk, Aline author Widschwendter, Martin author Bowtell, David D L author Candido Dos Reis, Francisco J author Cook, Linda S author Fortner, Renée T author García, María J author Harris, Holly R author Huntsman, David G author Karnezis, Anthony N author Köbel, Martin author Menon, Usha author Pharoah, Paul D P author Doherty, Jennifer A author Anglesio, Michael S author Pike, Malcolm C author Pearce, Celeste Leigh author Friedlander, Michael L author DeFazio, Anna author Nelson, Brad H author Ramus, Susan J author 2023-01 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. Gynecol Oncol . 2023 Jan:168:23-31. Gynecol Oncol 36368129 https://hdl.handle.net/20.500.12105/26527 Immune infiltrate Mucinous ovarian carcinoma Rare histotype Profiling the immune landscape in mucinous ovarian carcinoma.