High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer

• Published in: Gynecologic oncology Vol. 159; no. 3; pp. 860 - 868
• Main Authors: Corvigno, Sara, Mezheyeuski, Artur, De La Fuente, Laura Martin, Westbom-Fremer, Sofia, Carlson, Joseph W., Fernebro, Josefin, Åvall-Lundqvist, Elisabeth, Kannisto, Paivi, Hedenfalk, Ingrid, Malander, Susanne, Rolny, Charlotte, Dahlstrand, Hanna, Östman, Arne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Cancer and Oncology; Cancer och onkologi; Carcinoma, Ovarian Epithelial - diagnosis; Carcinoma, Ovarian Epithelial - immunology; Carcinoma, Ovarian Epithelial - mortality; Carcinoma, Ovarian Epithelial - pathology; CD11c Antigen - metabolism; Clinical Medicine; Female; High-grade serous ovarian cancer; Humans; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Neoplasm Grading; Oncology; Onkologi; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - immunology; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Ovary - immunology; Ovary - pathology; Overall survival; Prognosis; Retrospective Studies; Sweden; Tumor immunology; Tumor microenvironment; Tumor Microenvironment - immunology; Tumor-associated macrophages; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; Sweden; Tumor microenvironment; Overall survival; High-grade serous ovarian cancer; Tumor-associated macrophages; Tumor immunology
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2020.09.041

Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC). A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort. CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23–0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22–0.93; p = 0.03). Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC. •We propose a novel analytical approach to score density of localization and marker-defined TAMs.•CD163+ TAMs were the most abundant in all compartments.•Intraepithelial density of CD80+ TAMs highly correlates with intraepithelial density of CD8+ cells.•High density of CD11c+ stroma localized macrophages is related to longer overall survival in two independent cohorts of HGSC.