High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer
(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.
(Less)
- author
- organization
- publishing date
- 2020-12-01
- 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}}, }