Sistema de Salut de Catalunya
Institut Català de la Salut
[Corvigno S, Martín-Bernabé A] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. [Fernebro J] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Department of Gynecologic Oncology, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden. [Severin Karlsson J] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden. [Mezheieusky A] IGP, Uppsala University, Sweden. Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Martin De La Fuente L] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University and Skåne University Hospital, Lund, Sweden
Vall d'Hebron Barcelona Hospital Campus
2025-04-01T07:34:50Z
2025-04-01T07:34:50Z
2025-02
Fibroblast; High-grade serous ovarian cancer; T cell
Fibroblastos; Cáncer de ovario seroso de alto grado; Célula T
Fibroblast; Càncer d'ovari serós d'alt grau; Cèl·lula T
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.
The study was supported by The Cancer Research Foundations of Radiumhemmet, The Swedish Cancer Society and Stockholm City Council.
Article
Published version
English
Fibroblasts; Ovaris - Càncer - Prognosi; Cèl·lules T; Adenocarcinoma - Prognosi; PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cystadenocarcinoma::Cystadenocarcinoma, Serous; ANATOMY::Cells::Connective Tissue Cells::Fibroblasts::Cancer-Associated Fibroblasts; ANATOMY::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::Hemic and Immune Systems::CD8-Positive T-Lymphocytes; DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms; FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::cistoadenocarcinoma::cistoadenocarcinoma seroso; ANATOMÍA::células::células del tejido conectivo::fibroblastos::fibroblastos asociados al cáncer; ANATOMÍA::sistemas sanguíneo e inmunológico::sangre::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::sistemas sanguíneo e inmunológico::linfocitos T CD8-positivos; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas
Elsevier
Gynecologic Oncology;193
https://doi.org/10.1016/j.ygyno.2025.01.010
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
