2022-RA-1007-ESGO High expression of FAP+ cancer-associated fibroblasts predict poor outcome in patients with high-grade serous ovarian cancer with high CD8-postive T-cell infiltration. (20th October 2022)

• Record Type: Journal Article
• Authors: Fernebro, Josefin; Corvigno, Sara; Mezheieusky, Arthur; Karlsson, Josefin Severin; Fuente, Laura Martin De La; Westbom-Fremer, Sofia M; Carlson, Joseph; Kannisto, Paivi M; Hedenfalk, Ingrid M; Malander, Susanne M; Östman, Arne; Dahlstrand, Hanna
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 2
• Page Start: A411
• Page End: A411
• Publication Date: 2022-10-20
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-ESGO.880
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Introduction/Background: Tumor biology studies have implied that fibroblasts act as negative regulators of immune cell function in cancer. We investigated the impact of FAP-positive cells in high-grade serous ovarian cancer (HGSC) in relation to CD8 expression. Methodology: A discovery cohort (N=113) of HGSC was subjected to immunohistochemistry (IHC) of FAP and CD8. Marker status was correlated with overall survival (OS) and progression-free survival (PFS). Findings were confirmed in a validation cohort (N=121) and in public available datasets (TCGA and GSE9891). Results: We confirmed previous findings that high density of CD8+ cells in HGSC is associated with longer OS compared to low density (HR 0.55; 95% CI 0.33–0.85; p=0.008). In the discovery cohort high intensity of FAP was associated with shorter median PFS in cases with high density of stromal CD8+ cells (11.4 versus 18.6 months) compared to low intensity of FAP (p=0.007). In contrast, high intensity of FAP was not associated with PFS in cases with low density of CD8+ cells. In the validation cohort, high intensity of FAP in the patients with high density of stromal CD8+ cells was associated with shorter OS compared to low intensity of FAP (p=0.01). This association was not seen in the cases with low density of CD8+ cells. The association between high FAP expression and poor outcome in the high density CD8+ group was confirmed in two independent gene-expression data sets, with a shorter PFS in the TCGA dataset and shorter PFS and OS in the GSE9891 dataset. Conclusion: The study shows a specific FAP positive fibroblast-subset of cases with poor prognosis restricted to a CD8 high density group of HGSC. Therapy targeting the immunosuppressive action of fibroblasts may be a tool to enhance the known positive prognostic effect of CD8-cells in ovarian cancer and may be explored in T-cell depended immune therapy.