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

Objective: 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).
Methods: 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.
Results: 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).
Conclusions: 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.
Competing Interests: Declaration of Competing Interest LMF and SC have received funding from Roche in collaboration with the Swedish Society of Gynecological Oncology. JC has received funding from TermoFisher and Roche. SM has received funding from Astra Zeneca and Tesaro GSK. IH reports grants from The Swedish Cancer Society, The Cancer and Allergy Foundation, grants from Mrs. B Kamprad Foundation, and from King Gustaf V Foundation. EAL reports financial relationships with Roche, AstraZeneca, Clovis Oncology, Tesaro, Genmab. AÖ has received funding from EliLilly. The remaining authors have nothing to disclose.
(Copyright © 2020 Elsevier Inc. All rights reserved.)