High prevalence of FAP+ cancer-associated fibroblasts predicts poor outcome in patients with high-grade serous ovarian cancer with high CD8 T-cell density
Copyright policy )High prevalence of FAP+ cancer-associated fibroblasts predicts poor outcome in patients with high-grade serous ovarian cancer with high CD8 T-cell density
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.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.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.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.
Adult, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cystadenocarcinoma::Cystadenocarcinoma, Serous, ANATOMÍA::células::células del tejido conectivo::fibroblastos::fibroblastos asociados al cáncer, CD8-Positive T-Lymphocytes, Adenocarcinoma - Prognosi, ANATOMY::Cells::Connective Tissue Cells::Fibroblasts::Cancer-Associated Fibroblasts, Cohort Studies, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::cistoadenocarcinoma::cistoadenocarcinoma seroso, Lymphocytes, Tumor-Infiltrating, Cancer-Associated Fibroblasts, Endopeptidases, Tumor Microenvironment, Humans, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico, Aged, Ovarian Neoplasms, Aged, 80 and over, Cancer och onkologi, ANATOMÍA::sistemas sanguíneo e inmunológico::sangre::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::sistemas sanguíneo e inmunológico::linfocitos T CD8-positivos, Serine Endopeptidases, FAP, T cell, Membrane Proteins, CD8, Fibroblasts, Middle Aged, ANATOMY::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::Hemic and Immune Systems::CD8-Positive T-Lymphocytes, Prognosis, Progression-Free Survival, Cystadenocarcinoma, Serous, Tumor microenvironment, Cèl·lules T, Gelatinases, Cancer and Oncology, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas, Ovaris - Càncer - Prognosi, Fibroblast, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis, Female, DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms, Neoplasm Grading, High-grade serous ovarian cancer
Adult, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Cystadenocarcinoma::Cystadenocarcinoma, Serous, ANATOMÍA::células::células del tejido conectivo::fibroblastos::fibroblastos asociados al cáncer, CD8-Positive T-Lymphocytes, Adenocarcinoma - Prognosi, ANATOMY::Cells::Connective Tissue Cells::Fibroblasts::Cancer-Associated Fibroblasts, Cohort Studies, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma::cistoadenocarcinoma::cistoadenocarcinoma seroso, Lymphocytes, Tumor-Infiltrating, Cancer-Associated Fibroblasts, Endopeptidases, Tumor Microenvironment, Humans, FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico, Aged, Ovarian Neoplasms, Aged, 80 and over, Cancer och onkologi, ANATOMÍA::sistemas sanguíneo e inmunológico::sangre::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::sistemas sanguíneo e inmunológico::linfocitos T CD8-positivos, Serine Endopeptidases, FAP, T cell, Membrane Proteins, CD8, Fibroblasts, Middle Aged, ANATOMY::Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::Hemic and Immune Systems::CD8-Positive T-Lymphocytes, Prognosis, Progression-Free Survival, Cystadenocarcinoma, Serous, Tumor microenvironment, Cèl·lules T, Gelatinases, Cancer and Oncology, PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas, Ovaris - Càncer - Prognosi, Fibroblast, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis, Female, DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms, Neoplasm Grading, High-grade serous ovarian cancer
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