Meagher, Nicola SHamilton, PhineasMilne, KatyThornton, ShelbyHarris, BronwynWeir, AshleyAlsop, JenniferBisinoto, ChristianiBrenton, James DBrooks-Wilson, AngelaChiu, Derek SCushing-Haugen, Kara LFereday, SianGarsed, Dale WGayther, Simon AGentry-Maharaj, AleksandraGilks, BlakeJimenez-Linan, MercedesKennedy, Catherine JLe, Nhu DPiskorz, Anna MRiggan, Marjorie JShah, MitulSingh, NaveenaTalhouk, AlineWidschwendter, MartinBowtell, David D LCandido Dos Reis, Francisco JCook, Linda SFortner, Renée TGarcía, María JHarris, Holly RHuntsman, David GKarnezis, Anthony NKöbel, MartinMenon, UshaPharoah, Paul D PDoherty, Jennifer AAnglesio, Michael SPike, Malcolm CPearce, Celeste LeighFriedlander, Michael LDeFazio, AnnaNelson, Brad HRamus, Susan J2025-03-202025-03-202023-01Gynecol Oncol . 2023 Jan:168:23-31.https://hdl.handle.net/20.500.12105/26527Funding This work was supported by the U.S. Army Medical Research and Materiel Command through the Ovarian Cancer Research Program under Award No. W81XWH-16-2-0010. We are grateful for financial support for this study from UNSW Faculty of Medicine and Health. Funding for this study came from the accelerator grant of NSW Health PhD Scholarship Program awarded to Nicola S Meagher.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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Immune infiltrateMucinous ovarian carcinomaRare histotypeAttribution-NonCommercial-NoDerivatives 4.0 International3636812916823-31Gynecol Oncolopen access