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High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer
Karolinska Inst, Sweden; Uppsala Univ, Sweden.
Karolinska Inst, Sweden; Uppsala Univ, Sweden.
Lund Univ, Sweden; Skane Univ Hosp, Sweden.
Lund Univ, Sweden; Skane Univ Hosp, Sweden.
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2020 (English)In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 159, no 3, p. 860-868Article in journal (Refereed) Published
Abstract [en]

Objective. Pre-clinical studies have identified markerand 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-, CD80and 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 markerand localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC. (C) 2020 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2020. Vol. 159, no 3, p. 860-868
Keywords [en]
High-grade serous ovarian cancer; Tumor microenvironment; Tumor-associated macrophages; Tumor immunology; Overall survival
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-173206DOI: 10.1016/j.ygyno.2020.09.041ISI: 000596721200039PubMedID: 33032823OAI: oai:DiVA.org:liu-173206DiVA, id: diva2:1527390
Note

Funding Agencies|Cancer Research Foundations of Radiumhemmet; Swedish Research Council (STARGET Linne grant)Swedish Research Council; Swedish Cancer SocietySwedish Cancer Society; Stockholm City Council

Available from: 2021-02-10 Created: 2021-02-10 Last updated: 2021-02-10

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Åvall Lundqvist, Elisabeth
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of Oncology
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