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

Corvigno, Sara ; Mezheyeuski, Artur ; De La Fuente, Laura Martin LU ; Westbom-Fremer, Sofia LU orcid ; Carlson, Joseph W. ; Fernebro, Josefin LU ; Åvall-Lundqvist, Elisabeth ; Kannisto, Paivi LU ; Hedenfalk, Ingrid LU orcid and Malander, Susanne LU orcid , et al. (2020) In Gynecologic Oncology 159(3). p.860-868
Abstract

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:... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
High-grade serous ovarian cancer, Overall survival, Tumor immunology, Tumor microenvironment, Tumor-associated macrophages
in
Gynecologic Oncology
volume
159
issue
3
pages
9 pages
publisher
Academic Press
external identifiers
  • pmid:33032823
  • scopus:85092107932
ISSN
0090-8258
DOI
10.1016/j.ygyno.2020.09.041
language
English
LU publication?
yes
id
5d86aedf-1364-49ba-8da6-194ad5dd11bd
date added to LUP
2020-10-22 17:19:13
date last changed
2024-04-17 18:54:10
@article{5d86aedf-1364-49ba-8da6-194ad5dd11bd,
  abstract     = {{<p>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<sup>+</sup> 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.</p>}},
  author       = {{Corvigno, Sara and Mezheyeuski, Artur and De La Fuente, Laura Martin and Westbom-Fremer, Sofia and Carlson, Joseph W. and Fernebro, Josefin and Åvall-Lundqvist, Elisabeth and Kannisto, Paivi and Hedenfalk, Ingrid and Malander, Susanne and Rolny, Charlotte and Dahlstrand, Hanna and Östman, Arne}},
  issn         = {{0090-8258}},
  keywords     = {{High-grade serous ovarian cancer; Overall survival; Tumor immunology; Tumor microenvironment; Tumor-associated macrophages}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{3}},
  pages        = {{860--868}},
  publisher    = {{Academic Press}},
  series       = {{Gynecologic Oncology}},
  title        = {{High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer}},
  url          = {{http://dx.doi.org/10.1016/j.ygyno.2020.09.041}},
  doi          = {{10.1016/j.ygyno.2020.09.041}},
  volume       = {{159}},
  year         = {{2020}},
}