Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

High prevalence of FAP+ cancer-associated fibroblasts predicts poor outcome in patients with high-grade serous ovarian cancer with high CD8 T-cell density

Corvigno, Sara ; Fernebro, Josefin LU ; Karlsson, Josefin Severin ; Mezheieusky, Artur ; Martín-Bernabé, Alfonso ; De La Fuente, Laura Martin LU ; Westbom-Fremer, Sofia LU orcid ; Carlson, Joseph W. ; Klein, Christian and Kannisto, Paivi LU , et al. (2025) In Gynecologic Oncology 193. p.148-155
Abstract

Objective: Studies have implied that fibroblasts may act as regulators of immune cells in the tumor microenvironment (TME). We investigated the clinical relevance of fibroblast activation protein (FAP) positive stroma in high-grade serous ovarian cancer (HGSC) in relation to CD8+ lymphocyte's infiltration. 

Methods: In a discovery cohort (N = 113) of HGSC, expression of FAP and CD8 in the TME was analyzed with immunohistochemistry. Results were correlated with overall survival (OS) and progression-free survival (PFS). The findings were validated in an independent cohort of HGSC (N = 121) and in public available datasets. 

Results: High infiltration of CD8+ cells in the TME of HGSC was found to be associated with longer OS,... (More)

Objective: Studies have implied that fibroblasts may act as regulators of immune cells in the tumor microenvironment (TME). We investigated the clinical relevance of fibroblast activation protein (FAP) positive stroma in high-grade serous ovarian cancer (HGSC) in relation to CD8+ lymphocyte's infiltration. 

Methods: In a discovery cohort (N = 113) of HGSC, expression of FAP and CD8 in the TME was analyzed with immunohistochemistry. Results were correlated with overall survival (OS) and progression-free survival (PFS). The findings were validated in an independent cohort of HGSC (N = 121) and in public available datasets. 

Results: High infiltration of CD8+ cells in the TME of HGSC was found to be associated with longer OS, as previously known. Increased expression of FAP was associated with shorter median PFS (11.4 vs. 18.6 months) in tumors with high density of CD8+ cells (HR 4.03, CI 95 % 1.38–11.72, p = 0.01). Similarly, in the validation cohort, high intensity of FAP in cases with high density of CD8+ cells was associated with shorter OS, 31.5 vs 76.9 months (HR 2.83; 95 % CI 1.17–6.86, p = 0.02). The results were consistent in multivariable analyses. The association between high FAP expression and poor outcome in high density CD8 HGSC was also confirmed in publicly available datasets. 

Conclusions: The TME infiltration of FAP-positive fibroblasts is associated with poor prognosis in HGSC with high CD8+ cells density. Targeting the FAP+ subset of fibroblasts may unlock the local immune-activation in the TME thus enhance the positive prognostic effect of T-cells in ovarian cancer.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CD8, FAP, Fibroblast, High-grade serous ovarian cancer, T cell, Tumor microenvironment
in
Gynecologic Oncology
volume
193
pages
148 - 155
publisher
Academic Press
external identifiers
  • scopus:85216850665
  • pmid:39914230
ISSN
0090-8258
DOI
10.1016/j.ygyno.2025.01.010
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Authors
id
387c53a6-453f-4b35-8551-03b865812dc3
date added to LUP
2025-03-03 10:02:52
date last changed
2025-07-08 07:30:16
@article{387c53a6-453f-4b35-8551-03b865812dc3,
  abstract     = {{<p>Objective: Studies have implied that fibroblasts may act as regulators of immune cells in the tumor microenvironment (TME). We investigated the clinical relevance of fibroblast activation protein (FAP) positive stroma in high-grade serous ovarian cancer (HGSC) in relation to CD8+ lymphocyte's infiltration. </p><p>Methods: In a discovery cohort (N = 113) of HGSC, expression of FAP and CD8 in the TME was analyzed with immunohistochemistry. Results were correlated with overall survival (OS) and progression-free survival (PFS). The findings were validated in an independent cohort of HGSC (N = 121) and in public available datasets. </p><p>Results: High infiltration of CD8+ cells in the TME of HGSC was found to be associated with longer OS, as previously known. Increased expression of FAP was associated with shorter median PFS (11.4 vs. 18.6 months) in tumors with high density of CD8+ cells (HR 4.03, CI 95 % 1.38–11.72, p = 0.01). Similarly, in the validation cohort, high intensity of FAP in cases with high density of CD8+ cells was associated with shorter OS, 31.5 vs 76.9 months (HR 2.83; 95 % CI 1.17–6.86, p = 0.02). The results were consistent in multivariable analyses. The association between high FAP expression and poor outcome in high density CD8 HGSC was also confirmed in publicly available datasets. </p><p>Conclusions: The TME infiltration of FAP-positive fibroblasts is associated with poor prognosis in HGSC with high CD8+ cells density. Targeting the FAP+ subset of fibroblasts may unlock the local immune-activation in the TME thus enhance the positive prognostic effect of T-cells in ovarian cancer.</p>}},
  author       = {{Corvigno, Sara and Fernebro, Josefin and Karlsson, Josefin Severin and Mezheieusky, Artur and Martín-Bernabé, Alfonso and De La Fuente, Laura Martin and Westbom-Fremer, Sofia and Carlson, Joseph W. and Klein, Christian and Kannisto, Paivi and Hedenfalk, Ingrid and Malander, Susanne and Östman, Arne and Dahlstrand, Hanna}},
  issn         = {{0090-8258}},
  keywords     = {{CD8; FAP; Fibroblast; High-grade serous ovarian cancer; T cell; Tumor microenvironment}},
  language     = {{eng}},
  pages        = {{148--155}},
  publisher    = {{Academic Press}},
  series       = {{Gynecologic Oncology}},
  title        = {{High prevalence of FAP+ cancer-associated fibroblasts predicts poor outcome in patients with high-grade serous ovarian cancer with high CD8 T-cell density}},
  url          = {{http://dx.doi.org/10.1016/j.ygyno.2025.01.010}},
  doi          = {{10.1016/j.ygyno.2025.01.010}},
  volume       = {{193}},
  year         = {{2025}},
}